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2011
Chtarbanova Stanislava, Imler Jean-Luc
Microbial sensing by Toll receptors: a historical perspective Journal Article
In: Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 31, no. 8, pp. 1734–1738, 2011, ISSN: 1524-4636.
Abstract | Links | BibTeX | Tags: Animals, Cardiovascular Diseases, history, Host-Pathogen Interactions, Humans, imler, Immunity, Innate, M3i, Macrophages, Toll-Like Receptors
@article{chtarbanova_microbial_2011,
title = {Microbial sensing by Toll receptors: a historical perspective},
author = {Stanislava Chtarbanova and Jean-Luc Imler},
doi = {10.1161/ATVBAHA.108.179523},
issn = {1524-4636},
year = {2011},
date = {2011-08-01},
journal = {Arteriosclerosis, Thrombosis, and Vascular Biology},
volume = {31},
number = {8},
pages = {1734--1738},
abstract = {The family of Toll-like receptors plays an essential role in the induction of the immune response. These receptors sense the presence of microbial ligands and activate the nuclear factor-κB transcription factor. We review the key studies that led from the formulation of the concept of pattern recognition receptors to the characterization of Toll-like receptors, insisting on the important role played by the model organism Drosophila melanogaster and on the increasing evidence connecting these receptors to cardiovascular disease.},
keywords = {Animals, Cardiovascular Diseases, history, Host-Pathogen Interactions, Humans, imler, Immunity, Innate, M3i, Macrophages, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
The family of Toll-like receptors plays an essential role in the induction of the immune response. These receptors sense the presence of microbial ligands and activate the nuclear factor-κB transcription factor. We review the key studies that led from the formulation of the concept of pattern recognition receptors to the characterization of Toll-like receptors, insisting on the important role played by the model organism Drosophila melanogaster and on the increasing evidence connecting these receptors to cardiovascular disease.
Eleftherianos Ioannis, Won Sungyong, Chtarbanova Stanislava, Squiban Barbara, Ocorr Karen, Bodmer Rolf, Beutler Bruce, Hoffmann Jules A, Imler Jean-Luc
ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 29, pp. 12024–12029, 2011, ISSN: 1091-6490.
Abstract | Links | BibTeX | Tags: Animals, Heart, HeLa Cells, hoffmann, Humans, imler, Immunity, Immunoblotting, Inbred C57BL, Innate, KATP Channels, M3i, Mice, Nodaviridae, Pinacidil, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Tolbutamide, Viral Load, Viremia
@article{eleftherianos_atp-sensitive_2011,
title = {ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections},
author = {Ioannis Eleftherianos and Sungyong Won and Stanislava Chtarbanova and Barbara Squiban and Karen Ocorr and Rolf Bodmer and Bruce Beutler and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1073/pnas.1108926108},
issn = {1091-6490},
year = {2011},
date = {2011-07-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {108},
number = {29},
pages = {12024--12029},
abstract = {The effects of the cellular environment on innate immunity remain poorly characterized. Here, we show that in Drosophila ATP-sensitive potassium channels (K(ATP)) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV). FHV viral load in the heart rapidly increases in K(ATP) mutant flies, leading to increased viremia and accelerated death. The effect of K(ATP) channels is dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an activity associated with this potassium channel participates in this antiviral pathway in Drosophila. Flies treated with the K(ATP) agonist drug pinacidil are protected against FHV infection, thus demonstrating the importance of this regulation of innate immunity by the cellular environment in the heart. In mice, the Coxsackievirus B3 replicates to higher titers in the hearts of mayday mutant animals, which are deficient in the Kir6.1 subunit of K(ATP) channels, than in controls. Together, our data suggest that K(ATP) channel deregulation can have a critical impact on innate antiviral immunity in the heart.},
keywords = {Animals, Heart, HeLa Cells, hoffmann, Humans, imler, Immunity, Immunoblotting, Inbred C57BL, Innate, KATP Channels, M3i, Mice, Nodaviridae, Pinacidil, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Tolbutamide, Viral Load, Viremia},
pubstate = {published},
tppubtype = {article}
}
The effects of the cellular environment on innate immunity remain poorly characterized. Here, we show that in Drosophila ATP-sensitive potassium channels (K(ATP)) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV). FHV viral load in the heart rapidly increases in K(ATP) mutant flies, leading to increased viremia and accelerated death. The effect of K(ATP) channels is dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an activity associated with this potassium channel participates in this antiviral pathway in Drosophila. Flies treated with the K(ATP) agonist drug pinacidil are protected against FHV infection, thus demonstrating the importance of this regulation of innate immunity by the cellular environment in the heart. In mice, the Coxsackievirus B3 replicates to higher titers in the hearts of mayday mutant animals, which are deficient in the Kir6.1 subunit of K(ATP) channels, than in controls. Together, our data suggest that K(ATP) channel deregulation can have a critical impact on innate antiviral immunity in the heart.
2009
Kemp Cordula, Imler Jean-Luc
Antiviral immunity in drosophila Journal Article
In: Current Opinion in Immunology, vol. 21, no. 1, pp. 3–9, 2009, ISSN: 1879-0372.
Abstract | Links | BibTeX | Tags: Animals, Argonaute Proteins, Caspases, DEAD-box RNA Helicases, Evolution, Gene Expression Regulation, Host-Pathogen Interactions, imler, M3i, Membrane Proteins, Molecular, Nuclear Proteins, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Virus Infections, RNA Viruses, RNA-Induced Silencing Complex, Viral, Virulence
@article{kemp_antiviral_2009,
title = {Antiviral immunity in drosophila},
author = {Cordula Kemp and Jean-Luc Imler},
doi = {10.1016/j.coi.2009.01.007},
issn = {1879-0372},
year = {2009},
date = {2009-02-01},
journal = {Current Opinion in Immunology},
volume = {21},
number = {1},
pages = {3--9},
abstract = {Genetic analysis of the drosophila antiviral response indicates that RNA interference plays a major role. This contrasts with the situation in mammals, where interferon-induced responses mediate innate antiviral host-defense. An inducible response also contributes to antiviral immunity in drosophila, and similarities in the sensing and signaling of viral infection are becoming apparent between drosophila and mammals. In particular, DExD/H box helicases appear to play a crucial role in the cytosolic detection of viral RNAs in flies and mammals.},
keywords = {Animals, Argonaute Proteins, Caspases, DEAD-box RNA Helicases, Evolution, Gene Expression Regulation, Host-Pathogen Interactions, imler, M3i, Membrane Proteins, Molecular, Nuclear Proteins, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Virus Infections, RNA Viruses, RNA-Induced Silencing Complex, Viral, Virulence},
pubstate = {published},
tppubtype = {article}
}
Genetic analysis of the drosophila antiviral response indicates that RNA interference plays a major role. This contrasts with the situation in mammals, where interferon-induced responses mediate innate antiviral host-defense. An inducible response also contributes to antiviral immunity in drosophila, and similarities in the sensing and signaling of viral infection are becoming apparent between drosophila and mammals. In particular, DExD/H box helicases appear to play a crucial role in the cytosolic detection of viral RNAs in flies and mammals.
Berry Bassam, Deddouche Safia, Kirschner Doris, Imler Jean-Luc, Antoniewski Christophe
Viral suppressors of RNA silencing hinder exogenous and endogenous small RNA pathways in Drosophila Journal Article
In: PloS One, vol. 4, no. 6, pp. e5866, 2009, ISSN: 1932-6203.
Abstract | Links | BibTeX | Tags: Animals, Antiviral Agents, Crosses, Double-Stranded, Gene Silencing, Genetic, Genetically Modified, Heterozygote, imler, Invertebrate, M3i, Photoreceptor Cells, Reverse Transcriptase Polymerase Chain Reaction, RNA, RNA Interference, Transgenes
@article{berry_viral_2009,
title = {Viral suppressors of RNA silencing hinder exogenous and endogenous small RNA pathways in Drosophila},
author = {Bassam Berry and Safia Deddouche and Doris Kirschner and Jean-Luc Imler and Christophe Antoniewski},
doi = {10.1371/journal.pone.0005866},
issn = {1932-6203},
year = {2009},
date = {2009-01-01},
journal = {PloS One},
volume = {4},
number = {6},
pages = {e5866},
abstract = {BACKGROUND: In plants and insects, RNA interference (RNAi) is the main responder against viruses and shapes the basis of antiviral immunity. Viruses counter this defense by expressing viral suppressors of RNAi (VSRs). While VSRs in Drosophila melanogaster were shown to inhibit RNAi through different modes of action, whether they act on other silencing pathways remained unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that expression of various plant and insect VSRs in transgenic flies does not perturb the Drosophila microRNA (miRNA) pathway; but in contrast, inhibits antiviral RNAi and the RNA silencing response triggered by inverted repeat transcripts, and injection of dsRNA or siRNA. Strikingly, these VSRs also suppressed transposon silencing by endogenous siRNAs (endo-siRNAs). CONCLUSIONS/SIGNIFICANCE: Our findings identify VSRs as tools to unravel small RNA pathways in insects and suggest a cosuppression of antiviral RNAi and endo-siRNA silencing by viruses during fly infections.},
keywords = {Animals, Antiviral Agents, Crosses, Double-Stranded, Gene Silencing, Genetic, Genetically Modified, Heterozygote, imler, Invertebrate, M3i, Photoreceptor Cells, Reverse Transcriptase Polymerase Chain Reaction, RNA, RNA Interference, Transgenes},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: In plants and insects, RNA interference (RNAi) is the main responder against viruses and shapes the basis of antiviral immunity. Viruses counter this defense by expressing viral suppressors of RNAi (VSRs). While VSRs in Drosophila melanogaster were shown to inhibit RNAi through different modes of action, whether they act on other silencing pathways remained unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that expression of various plant and insect VSRs in transgenic flies does not perturb the Drosophila microRNA (miRNA) pathway; but in contrast, inhibits antiviral RNAi and the RNA silencing response triggered by inverted repeat transcripts, and injection of dsRNA or siRNA. Strikingly, these VSRs also suppressed transposon silencing by endogenous siRNAs (endo-siRNAs). CONCLUSIONS/SIGNIFICANCE: Our findings identify VSRs as tools to unravel small RNA pathways in insects and suggest a cosuppression of antiviral RNAi and endo-siRNA silencing by viruses during fly infections.
2008
Deddouche Safia, Matt Nicolas, Budd Aidan, Mueller Stefanie, Kemp Cordula, Galiana-Arnoux Delphine, Dostert Catherine, Antoniewski Christophe, Hoffmann Jules A, Imler Jean-Luc
The DExD/Ħ-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila Journal Article
In: Nature Immunology, vol. 9, no. 12, pp. 1425–1432, 2008, ISSN: 1529-2916.
Abstract | Links | BibTeX | Tags: Amino Acid, Animals, Electrophoresis, Fat Body, Gene Expression Regulation, Genetic, Genetically Modified, hoffmann, Humans, imler, M3i, matt, Phylogeny, Polyacrylamide Gel, Reverse Transcriptase Polymerase Chain Reaction, Ribonuclease III, RNA Helicases, Sequence Homology, Transcription, Virus Diseases
@article{deddouche_dexd/h-box_2008,
title = {The DExD/Ħ-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila},
author = {Safia Deddouche and Nicolas Matt and Aidan Budd and Stefanie Mueller and Cordula Kemp and Delphine Galiana-Arnoux and Catherine Dostert and Christophe Antoniewski and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1038/ni.1664},
issn = {1529-2916},
year = {2008},
date = {2008-12-01},
journal = {Nature Immunology},
volume = {9},
number = {12},
pages = {1425--1432},
abstract = {Drosophila, like other invertebrates and plants, relies mainly on RNA interference for its defense against viruses. In flies, viral infection also triggers the expression of many genes. One of the genes induced, Vago, encodes a 18-kilodalton cysteine-rich polypeptide. Here we provide genetic evidence that the Vago gene product controlled viral load in the fat body after infection with drosophila C virus. Induction of Vago was dependent on the helicase Dicer-2. Dicer-2 belongs to the same DExD/H-box helicase family as do the RIG-I-like receptors, which sense viral infection and mediate interferon induction in mammals. We propose that this family represents an evolutionary conserved set of sensors that detect viral nucleic acids and direct antiviral responses.},
keywords = {Amino Acid, Animals, Electrophoresis, Fat Body, Gene Expression Regulation, Genetic, Genetically Modified, hoffmann, Humans, imler, M3i, matt, Phylogeny, Polyacrylamide Gel, Reverse Transcriptase Polymerase Chain Reaction, Ribonuclease III, RNA Helicases, Sequence Homology, Transcription, Virus Diseases},
pubstate = {published},
tppubtype = {article}
}
Drosophila, like other invertebrates and plants, relies mainly on RNA interference for its defense against viruses. In flies, viral infection also triggers the expression of many genes. One of the genes induced, Vago, encodes a 18-kilodalton cysteine-rich polypeptide. Here we provide genetic evidence that the Vago gene product controlled viral load in the fat body after infection with drosophila C virus. Induction of Vago was dependent on the helicase Dicer-2. Dicer-2 belongs to the same DExD/H-box helicase family as do the RIG-I-like receptors, which sense viral infection and mediate interferon induction in mammals. We propose that this family represents an evolutionary conserved set of sensors that detect viral nucleic acids and direct antiviral responses.
Huszar Tünde, Imler Jean-Luc
Drosophila viruses and the study of antiviral host-defense Journal Article
In: Advances in Virus Research, vol. 72, pp. 227–265, 2008, ISSN: 0065-3527.
Abstract | Links | BibTeX | Tags: Animals, Host-Pathogen Interactions, imler, Immunity, Innate, Insect Viruses, M3i, RNA Interference, RNA Viruses
@article{huszar_drosophila_2008,
title = {Drosophila viruses and the study of antiviral host-defense},
author = {Tünde Huszar and Jean-Luc Imler},
doi = {10.1016/S0065-3527(08)00406-5},
issn = {0065-3527},
year = {2008},
date = {2008-01-01},
journal = {Advances in Virus Research},
volume = {72},
pages = {227--265},
abstract = {The fruit fly Drosophila melanogaster is a powerful model to study host-pathogen interactions. Most studies so far have focused on extracellular pathogens such as bacteria and fungi. More recently, viruses have come to the front, and RNA interference was shown to play a critical role in the control of viral infections in drosophila. We review here our current knowledge on drosophila viruses. A diverse set of RNA viruses belonging to several families (Rhabdoviridae, Dicistroviridae, Birnaviridae, Reoviridae, Errantiviridae) has been reported in D. melanogaster. By contrast, no DNA virus has been recovered up to now. The drosophila viruses represent powerful tools to study virus-cell interactions in vivo. Analysis of the literature however reveals that for many of them, important gaps exist in our understanding of their replication cycle, genome organization, morphology or pathogenesis. The data obtained in the past few years on antiviral defense mechanisms in drosophila, which point to evolutionary conserved pathways, highlight the potential of the D. melanogaster model to study antiviral innate immunity and to better understand the complex interaction between arthropod-borne viruses and their insect vectors.},
keywords = {Animals, Host-Pathogen Interactions, imler, Immunity, Innate, Insect Viruses, M3i, RNA Interference, RNA Viruses},
pubstate = {published},
tppubtype = {article}
}
The fruit fly Drosophila melanogaster is a powerful model to study host-pathogen interactions. Most studies so far have focused on extracellular pathogens such as bacteria and fungi. More recently, viruses have come to the front, and RNA interference was shown to play a critical role in the control of viral infections in drosophila. We review here our current knowledge on drosophila viruses. A diverse set of RNA viruses belonging to several families (Rhabdoviridae, Dicistroviridae, Birnaviridae, Reoviridae, Errantiviridae) has been reported in D. melanogaster. By contrast, no DNA virus has been recovered up to now. The drosophila viruses represent powerful tools to study virus-cell interactions in vivo. Analysis of the literature however reveals that for many of them, important gaps exist in our understanding of their replication cycle, genome organization, morphology or pathogenesis. The data obtained in the past few years on antiviral defense mechanisms in drosophila, which point to evolutionary conserved pathways, highlight the potential of the D. melanogaster model to study antiviral innate immunity and to better understand the complex interaction between arthropod-borne viruses and their insect vectors.
2007
Ferrandon Dominique, Imler Jean-Luc, Hetru Charles, Hoffmann Jules A
The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections Journal Article
In: Nat Rev Immunol, vol. 7, pp. 862–74, 2007.
Abstract | BibTeX | Tags: Animals, Bacterial Infections/*immunology/microbiology, Drosophila melanogaster/genetics/*immunology/microbiology, ferrandon, hoffmann, imler, Immunity, M3i, Mycoses/*immunology/microbiology, Natural/genetics, Signal Transduction/genetics/*immunology
@article{ferrandon_drosophila_2007b,
title = {The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections},
author = {Dominique Ferrandon and Jean-Luc Imler and Charles Hetru and Jules A Hoffmann},
year = {2007},
date = {2007-11-01},
journal = {Nat Rev Immunol},
volume = {7},
pages = {862--74},
abstract = {A hallmark of the potent, multifaceted antimicrobial defence of Drosophila melanogaster is the challenge-induced synthesis of several families of antimicrobial peptides by cells in the fat body. The basic mechanisms of recognition of various types of microbial infections by the adult fly are now understood, often in great detail. We have further gained valuable insight into the infection-induced gene reprogramming by nuclear factor-kappaB (NF-kappaB) family members under the dependence of complex intracellular signalling cascades. The striking parallels between the adult fly response and mammalian innate immune defences described below point to a common ancestry and validate the relevance of the fly defence as a paradigm for innate immunity.},
keywords = {Animals, Bacterial Infections/*immunology/microbiology, Drosophila melanogaster/genetics/*immunology/microbiology, ferrandon, hoffmann, imler, Immunity, M3i, Mycoses/*immunology/microbiology, Natural/genetics, Signal Transduction/genetics/*immunology},
pubstate = {published},
tppubtype = {article}
}
A hallmark of the potent, multifaceted antimicrobial defence of Drosophila melanogaster is the challenge-induced synthesis of several families of antimicrobial peptides by cells in the fat body. The basic mechanisms of recognition of various types of microbial infections by the adult fly are now understood, often in great detail. We have further gained valuable insight into the infection-induced gene reprogramming by nuclear factor-kappaB (NF-kappaB) family members under the dependence of complex intracellular signalling cascades. The striking parallels between the adult fly response and mammalian innate immune defences described below point to a common ancestry and validate the relevance of the fly defence as a paradigm for innate immunity.
Beutler Bruce, Eidenschenk Celine, Crozat Karine, Imler Jean-Luc, Takeuchi Osamu, Hoffmann Jules A, Akira Shizuo
Genetic analysis of resistance to viral infection Journal Article
In: Nature Reviews. Immunology, vol. 7, no. 10, pp. 753–766, 2007, ISSN: 1474-1741.
Abstract | Links | BibTeX | Tags: Animals, Antiviral Agents, Disease Susceptibility, Drug Resistance, Eukaryotic Cells, hoffmann, Humans, imler, Immunity, M3i, Mutation, Viral, Virus Diseases, viruses
@article{beutler_genetic_2007,
title = {Genetic analysis of resistance to viral infection},
author = {Bruce Beutler and Celine Eidenschenk and Karine Crozat and Jean-Luc Imler and Osamu Takeuchi and Jules A Hoffmann and Shizuo Akira},
doi = {10.1038/nri2174},
issn = {1474-1741},
year = {2007},
date = {2007-10-01},
journal = {Nature Reviews. Immunology},
volume = {7},
number = {10},
pages = {753--766},
abstract = {As machines that reprogramme eukaryotic cells to suit their own purposes, viruses present a difficult problem for multicellular hosts, and indeed, have become one of the central pre-occupations of the immune system. Unable to permanently outpace individual viruses in an evolutionary footrace, higher eukaryotes have evolved broadly active mechanisms with which to sense viruses and suppress their proliferation. These mechanisms have recently been elucidated by a combination of forward and reverse genetic methods. Some of these mechanisms are clearly ancient, whereas others are relatively new. All are remarkably adept at discriminating self from non-self, and allow the host to cope with what might seem an impossible predicament.},
keywords = {Animals, Antiviral Agents, Disease Susceptibility, Drug Resistance, Eukaryotic Cells, hoffmann, Humans, imler, Immunity, M3i, Mutation, Viral, Virus Diseases, viruses},
pubstate = {published},
tppubtype = {article}
}
As machines that reprogramme eukaryotic cells to suit their own purposes, viruses present a difficult problem for multicellular hosts, and indeed, have become one of the central pre-occupations of the immune system. Unable to permanently outpace individual viruses in an evolutionary footrace, higher eukaryotes have evolved broadly active mechanisms with which to sense viruses and suppress their proliferation. These mechanisms have recently been elucidated by a combination of forward and reverse genetic methods. Some of these mechanisms are clearly ancient, whereas others are relatively new. All are remarkably adept at discriminating self from non-self, and allow the host to cope with what might seem an impossible predicament.
Müller Stefanie, Imler Jean-Luc
Dicing with viruses: microRNAs as antiviral factors Journal Article
In: Immunity, vol. 27, no. 1, pp. 1–3, 2007, ISSN: 1074-7613.
Abstract | Links | BibTeX | Tags: Animals, DEAD-box RNA Helicases, Endoribonucleases, imler, M3i, MicroRNAs, Ribonuclease III, RNA Interference, RNA Virus Infections
@article{muller_dicing_2007,
title = {Dicing with viruses: microRNAs as antiviral factors},
author = {Stefanie Müller and Jean-Luc Imler},
doi = {10.1016/j.immuni.2007.07.003},
issn = {1074-7613},
year = {2007},
date = {2007-07-01},
journal = {Immunity},
volume = {27},
number = {1},
pages = {1--3},
abstract = {In plants and invertebrates, Dicer genes play a critical role against infections by RNA viruses. In this issue, Otsuka et al. (2007) report that Dicer mutant mice are hypersusceptible to infection by the RNA virus VSV.},
keywords = {Animals, DEAD-box RNA Helicases, Endoribonucleases, imler, M3i, MicroRNAs, Ribonuclease III, RNA Interference, RNA Virus Infections},
pubstate = {published},
tppubtype = {article}
}
In plants and invertebrates, Dicer genes play a critical role against infections by RNA viruses. In this issue, Otsuka et al. (2007) report that Dicer mutant mice are hypersusceptible to infection by the RNA virus VSV.
Weber Alexander N R, Gangloff Monique, Moncrieffe Martin C, Hyvert Yann, Imler Jean-Luc, Gay Nicholas J
Role of the Spatzle Pro-domain in the generation of an active toll receptor ligand Journal Article
In: The Journal of Biological Chemistry, vol. 282, no. 18, pp. 13522–13531, 2007, ISSN: 0021-9258.
Abstract | Links | BibTeX | Tags: Animals, Cytokines, dimerization, imler, ligands, M3i, Post-Translational, Protein Binding, Protein Processing, Protein Structure, Signal Transduction, Tertiary, Toll-Like Receptors
@article{weber_role_2007,
title = {Role of the Spatzle Pro-domain in the generation of an active toll receptor ligand},
author = {Alexander N R Weber and Monique Gangloff and Martin C Moncrieffe and Yann Hyvert and Jean-Luc Imler and Nicholas J Gay},
doi = {10.1074/jbc.M700068200},
issn = {0021-9258},
year = {2007},
date = {2007-05-01},
journal = {The Journal of Biological Chemistry},
volume = {282},
number = {18},
pages = {13522--13531},
abstract = {The cytokine Spätzle is the ligand for Drosophila Toll, the prototype of an important family of membrane receptors that function in embryonic patterning and innate immunity. A dimeric precursor of Spätzle is processed by an endoprotease to produce a form (C-106) that cross-links Toll receptor ectodomains and establishes signaling. Here we show that before processing the pro-domain of Spätzle is required for correct biosynthesis and secretion. We mapped two loss-of-function mutations of Spätzle to a discrete site in the pro-domain and showed that the phenotype arises because of a defect in biosynthesis rather than signaling. We also report that the pro-domain and C-106 remain associated after cleavage and that this processed complex signals with the same characteristics as the C-terminal fragment. These results suggest that before activation the determinants on C-106 that bind specifically to Toll are sequestered by the pro-domain and that proteolytic processing causes conformational rearrangements that expose these determinants and enables binding to Toll. Furthermore, we show that the pro-domain is released when the Toll extracellular domain binds to the complex, a finding that has implications for the generation of a signaling-competent Toll dimer.},
keywords = {Animals, Cytokines, dimerization, imler, ligands, M3i, Post-Translational, Protein Binding, Protein Processing, Protein Structure, Signal Transduction, Tertiary, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
The cytokine Spätzle is the ligand for Drosophila Toll, the prototype of an important family of membrane receptors that function in embryonic patterning and innate immunity. A dimeric precursor of Spätzle is processed by an endoprotease to produce a form (C-106) that cross-links Toll receptor ectodomains and establishes signaling. Here we show that before processing the pro-domain of Spätzle is required for correct biosynthesis and secretion. We mapped two loss-of-function mutations of Spätzle to a discrete site in the pro-domain and showed that the phenotype arises because of a defect in biosynthesis rather than signaling. We also report that the pro-domain and C-106 remain associated after cleavage and that this processed complex signals with the same characteristics as the C-terminal fragment. These results suggest that before activation the determinants on C-106 that bind specifically to Toll are sequestered by the pro-domain and that proteolytic processing causes conformational rearrangements that expose these determinants and enables binding to Toll. Furthermore, we show that the pro-domain is released when the Toll extracellular domain binds to the complex, a finding that has implications for the generation of a signaling-competent Toll dimer.
Croker Ben, Crozat Karine, Berger Michael, Xia Yu, Sovath Sosathya, Schaffer Lana, Eleftherianos Ioannis, Imler Jean-Luc, Beutler Bruce
ATP-sensitive potassium channels mediate survival during infection in mammals and insects Journal Article
In: Nature Genetics, vol. 39, no. 12, pp. 1453–1460, 2007, ISSN: 1546-1718.
Abstract | Links | BibTeX | Tags: Animals, ATP-Binding Cassette Transporters, Cloning, Coronary Vessels, Crosses, Ethylnitrosourea, Genetic, Homozygote, imler, infection, Inwardly Rectifying, KATP Channels, Lipopolysaccharides, M3i, Mice, Molecular, Mutagenesis, Potassium Channels, Sulfonylurea Receptors
@article{croker_atp-sensitive_2007,
title = {ATP-sensitive potassium channels mediate survival during infection in mammals and insects},
author = {Ben Croker and Karine Crozat and Michael Berger and Yu Xia and Sosathya Sovath and Lana Schaffer and Ioannis Eleftherianos and Jean-Luc Imler and Bruce Beutler},
doi = {10.1038/ng.2007.25},
issn = {1546-1718},
year = {2007},
date = {2007-01-01},
journal = {Nature Genetics},
volume = {39},
number = {12},
pages = {1453--1460},
abstract = {Specific homeostatic mechanisms confer stability in innate immune responses, preventing injury or death from infection. Here we identify, from a screen of N-ethyl-N-nitrosourea-mutagenized mice, a mutation causing both profound susceptibility to infection by mouse cytomegalovirus and approximately 20,000-fold sensitization to lipopolysaccharide (LPS), poly(I.C) and immunostimulatory (CpG) DNA. The LPS hypersensitivity phenotype is not suppressed by mutations in Myd88, Trif, Tnf, Tnfrsf1a, Ifnb, Ifng or Stat1, genes contributing to LPS responses, and results from an abnormality extrinsic to hematopoietic cells. The phenotype is due to a null allele of Kcnj8, encoding Kir6.1, a protein that combines with SUR2 to form an ATP-sensitive potassium channel (K(ATP)) expressed in coronary artery smooth muscle and endothelial cells. In Drosophila melanogaster, suppression of dSUR by RNA interference similarly causes hypersensitivity to infection by flock house virus. Thus, K(ATP) evolved to serve a homeostatic function during infection, and in mammals it prevents coronary artery vasoconstriction induced by cytokines dependent on TLR and/or MDA5 immunoreceptors.},
keywords = {Animals, ATP-Binding Cassette Transporters, Cloning, Coronary Vessels, Crosses, Ethylnitrosourea, Genetic, Homozygote, imler, infection, Inwardly Rectifying, KATP Channels, Lipopolysaccharides, M3i, Mice, Molecular, Mutagenesis, Potassium Channels, Sulfonylurea Receptors},
pubstate = {published},
tppubtype = {article}
}
Specific homeostatic mechanisms confer stability in innate immune responses, preventing injury or death from infection. Here we identify, from a screen of N-ethyl-N-nitrosourea-mutagenized mice, a mutation causing both profound susceptibility to infection by mouse cytomegalovirus and approximately 20,000-fold sensitization to lipopolysaccharide (LPS), poly(I.C) and immunostimulatory (CpG) DNA. The LPS hypersensitivity phenotype is not suppressed by mutations in Myd88, Trif, Tnf, Tnfrsf1a, Ifnb, Ifng or Stat1, genes contributing to LPS responses, and results from an abnormality extrinsic to hematopoietic cells. The phenotype is due to a null allele of Kcnj8, encoding Kir6.1, a protein that combines with SUR2 to form an ATP-sensitive potassium channel (K(ATP)) expressed in coronary artery smooth muscle and endothelial cells. In Drosophila melanogaster, suppression of dSUR by RNA interference similarly causes hypersensitivity to infection by flock house virus. Thus, K(ATP) evolved to serve a homeostatic function during infection, and in mammals it prevents coronary artery vasoconstriction induced by cytokines dependent on TLR and/or MDA5 immunoreceptors.
Galiana-Arnoux Delphine, Deddouche Safia, Imler Jean-Luc
Immunité antivirale chez la drosophile Journal Article
In: Journal de la Société de Biologie, vol. 201, no. 4, pp. 359–365, 2007, ISSN: 1295-0661.
Links | BibTeX | Tags: imler, M3i
@article{galiana-arnoux_immunite_2007,
title = {Immunité antivirale chez la drosophile},
author = {Delphine Galiana-Arnoux and Safia Deddouche and Jean-Luc Imler},
url = {http://www.biologie-journal.org/10.1051/jbio:2007906},
doi = {10.1051/jbio:2007906},
issn = {1295-0661},
year = {2007},
date = {2007-01-01},
urldate = {2015-11-26},
journal = {Journal de la Société de Biologie},
volume = {201},
number = {4},
pages = {359--365},
keywords = {imler, M3i},
pubstate = {published},
tppubtype = {article}
}
Galiana-Arnoux Delphine, Deddouche Safia, Imler Jean-Luc
[Antiviral immunity in drosophila] Journal Article
In: Journal De La Société De Biologie, vol. 201, no. 4, pp. 359–365, 2007, ISSN: 1295-0661.
Abstract | Links | BibTeX | Tags: imler, M3i
@article{galiana-arnoux_[antiviral_2007,
title = {[Antiviral immunity in drosophila]},
author = {Delphine Galiana-Arnoux and Safia Deddouche and Jean-Luc Imler},
doi = {10.1051/jbio:2007906},
issn = {1295-0661},
year = {2007},
date = {2007-01-01},
journal = {Journal De La Société De Biologie},
volume = {201},
number = {4},
pages = {359--365},
abstract = {Viral diseases represent a constant threat and an important cause of mortality worldwide. We have developed a model to study the response to RNA virus infection in the fruit-fly drosophila. This insect is a good model to study the genetic bases of innate immunity, which constitutes the first level of host-defense in animals. We have shown that viral infection in drosophila triggers a response different from that to bacterial or fungal infections. Our data at this stage point to the existence of at least two types of antiviral defense mechanisms. On one hand, viral infection triggers a JAK-STAT dependent transcriptional response that leads to the expression of antiviral molecules that remain to be characterized. On the other hand, viral RNAs are recognized by Dicer-2 and degraded in siRNAs, thus inducing RNA interference and degradation of viral RNAs. Strikingly, the drosophila antiviral response evokes by some aspects the interferon response in mammals (JAK-STAT pathway) and antiviral defenses in plants (RNA interference).},
keywords = {imler, M3i},
pubstate = {published},
tppubtype = {article}
}
Viral diseases represent a constant threat and an important cause of mortality worldwide. We have developed a model to study the response to RNA virus infection in the fruit-fly drosophila. This insect is a good model to study the genetic bases of innate immunity, which constitutes the first level of host-defense in animals. We have shown that viral infection in drosophila triggers a response different from that to bacterial or fungal infections. Our data at this stage point to the existence of at least two types of antiviral defense mechanisms. On one hand, viral infection triggers a JAK-STAT dependent transcriptional response that leads to the expression of antiviral molecules that remain to be characterized. On the other hand, viral RNAs are recognized by Dicer-2 and degraded in siRNAs, thus inducing RNA interference and degradation of viral RNAs. Strikingly, the drosophila antiviral response evokes by some aspects the interferon response in mammals (JAK-STAT pathway) and antiviral defenses in plants (RNA interference).
2006
Evans J D, Aronstein K, Chen Y P, Hetru Charles, Imler Jean-Luc, Jiang H, Kanost M, Thompson G J, Zou Z, Hultmark D
Immune pathways and defence mechanisms in honey bees Apis mellifera Journal Article
In: Insect Molecular Biology, vol. 15, no. 5, pp. 645–656, 2006, ISSN: 0962-1075.
Abstract | Links | BibTeX | Tags: Animals, Bees, Carrier Proteins, Genome, imler, Immunity, Insect, Janus Kinases, M3i, Multigene Family, Serine Endopeptidases, Signal Transduction, STAT Transcription Factors, Toll-Like Receptors
@article{evans_immune_2006,
title = {Immune pathways and defence mechanisms in honey bees Apis mellifera},
author = {J D Evans and K Aronstein and Y P Chen and Charles Hetru and Jean-Luc Imler and H Jiang and M Kanost and G J Thompson and Z Zou and D Hultmark},
doi = {10.1111/j.1365-2583.2006.00682.x},
issn = {0962-1075},
year = {2006},
date = {2006-10-01},
journal = {Insect Molecular Biology},
volume = {15},
number = {5},
pages = {645--656},
abstract = {Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera. We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity. We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens.},
keywords = {Animals, Bees, Carrier Proteins, Genome, imler, Immunity, Insect, Janus Kinases, M3i, Multigene Family, Serine Endopeptidases, Signal Transduction, STAT Transcription Factors, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera. We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity. We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens.
Galiana-Arnoux Delphine, Dostert Catherine, Schneemann Anette, Hoffmann Jules A, Imler Jean-Luc
Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila Journal Article
In: Nature Immunology, vol. 7, no. 6, pp. 590–597, 2006, ISSN: 1529-2908.
Abstract | Links | BibTeX | Tags: Animals, Genetically Modified, hoffmann, imler, M3i, Mutation, Nodaviridae, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Viruses, Viral, Viral Proteins, Virus Replication
@article{galiana-arnoux_essential_2006,
title = {Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila},
author = {Delphine Galiana-Arnoux and Catherine Dostert and Anette Schneemann and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1038/ni1335},
issn = {1529-2908},
year = {2006},
date = {2006-06-01},
journal = {Nature Immunology},
volume = {7},
number = {6},
pages = {590--597},
abstract = {The fruit fly Drosophila melanogaster is a model system for studying innate immunity, including antiviral host defense. Infection with drosophila C virus triggers a transcriptional response that is dependent in part on the Jak kinase Hopscotch. Here we show that successful infection and killing of drosophila with the insect nodavirus flock house virus was strictly dependent on expression of the viral protein B2, a potent inhibitor of processing of double-stranded RNA mediated by the essential RNA interference factor Dicer. Conversely, flies with a loss-of-function mutation in the gene encoding Dicer-2 (Dcr-2) showed enhanced susceptibility to infection by flock house virus, drosophila C virus and Sindbis virus, members of three different families of RNA viruses. These data demonstrate the importance of RNA interference for controlling virus replication in vivo and establish Dcr-2 as a host susceptibility locus for virus infections.},
keywords = {Animals, Genetically Modified, hoffmann, imler, M3i, Mutation, Nodaviridae, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Viruses, Viral, Viral Proteins, Virus Replication},
pubstate = {published},
tppubtype = {article}
}
The fruit fly Drosophila melanogaster is a model system for studying innate immunity, including antiviral host defense. Infection with drosophila C virus triggers a transcriptional response that is dependent in part on the Jak kinase Hopscotch. Here we show that successful infection and killing of drosophila with the insect nodavirus flock house virus was strictly dependent on expression of the viral protein B2, a potent inhibitor of processing of double-stranded RNA mediated by the essential RNA interference factor Dicer. Conversely, flies with a loss-of-function mutation in the gene encoding Dicer-2 (Dcr-2) showed enhanced susceptibility to infection by flock house virus, drosophila C virus and Sindbis virus, members of three different families of RNA viruses. These data demonstrate the importance of RNA interference for controlling virus replication in vivo and establish Dcr-2 as a host susceptibility locus for virus infections.
Chen Li-Ying, Wang Juinn-Chin, Hyvert Yann, Lin Hui-Ping, Perrimon Norbert, Imler Jean-Luc, Hsu Jui-Chou
Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo Journal Article
In: Current biology: CB, vol. 16, no. 12, pp. 1183–1193, 2006, ISSN: 0960-9822.
Abstract | Links | BibTeX | Tags: Adaptor Proteins, Animals, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, imler, Immunity, Immunologic, Innate, M3i, Models, Mutation, Nonmammalian, Phenotype, Phosphoproteins, Receptors, Signal Transducing, Toll-Like Receptors, Transcription Factors, Zinc Fingers
@article{chen_weckle_2006,
title = {Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo},
author = {Li-Ying Chen and Juinn-Chin Wang and Yann Hyvert and Hui-Ping Lin and Norbert Perrimon and Jean-Luc Imler and Jui-Chou Hsu},
doi = {10.1016/j.cub.2006.05.050},
issn = {0960-9822},
year = {2006},
date = {2006-06-01},
journal = {Current biology: CB},
volume = {16},
number = {12},
pages = {1183--1193},
abstract = {BACKGROUND: The Drosophila Toll pathway takes part in both establishment of the embryonic dorsoventral axis and induction of the innate immune response in adults. Upon activation by the cytokine Spätzle, Toll interacts with the adaptor proteins DmMyD88 and Tube and the kinase Pelle and triggers degradation of the inhibitor Cactus, thus allowing the nuclear translocation of the transcription factor Dorsal/Dif. weckle (wek) was previously identified as a new dorsal group gene that encodes a putative zinc finger transcription factor. However, its role in the Toll pathway was unknown. RESULTS: Here, we isolated new wek alleles and demonstrated that cactus is epistatic to wek, which in turn is epistatic to Toll. Consistent with this, Wek localizes to the plasma membrane of embryos, independently of Toll signaling. Wek homodimerizes and associates with Toll. Moreover, Wek binds to and localizes DmMyD88 to the plasma membrane. Thus, Wek acts as an adaptor to assemble/stabilize a Toll/Wek/DmMyD88/Tube complex. Remarkably, unlike the DmMyD88/tube/pelle/cactus gene cassette of the Toll pathway, wek plays a minimal role, if any, in the immune defense against Gram-positive bacteria and fungi. CONCLUSIONS: We conclude that Wek is an adaptor to link Toll and DmMyD88 and is required for efficient recruitment of DmMyD88 to Toll. Unexpectedly, wek is dispensable for innate immune response, thus revealing differences in the Toll-mediated activation of Dorsal in the embryo and Dif in the fat body of adult flies.},
keywords = {Adaptor Proteins, Animals, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, imler, Immunity, Immunologic, Innate, M3i, Models, Mutation, Nonmammalian, Phenotype, Phosphoproteins, Receptors, Signal Transducing, Toll-Like Receptors, Transcription Factors, Zinc Fingers},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The Drosophila Toll pathway takes part in both establishment of the embryonic dorsoventral axis and induction of the innate immune response in adults. Upon activation by the cytokine Spätzle, Toll interacts with the adaptor proteins DmMyD88 and Tube and the kinase Pelle and triggers degradation of the inhibitor Cactus, thus allowing the nuclear translocation of the transcription factor Dorsal/Dif. weckle (wek) was previously identified as a new dorsal group gene that encodes a putative zinc finger transcription factor. However, its role in the Toll pathway was unknown. RESULTS: Here, we isolated new wek alleles and demonstrated that cactus is epistatic to wek, which in turn is epistatic to Toll. Consistent with this, Wek localizes to the plasma membrane of embryos, independently of Toll signaling. Wek homodimerizes and associates with Toll. Moreover, Wek binds to and localizes DmMyD88 to the plasma membrane. Thus, Wek acts as an adaptor to assemble/stabilize a Toll/Wek/DmMyD88/Tube complex. Remarkably, unlike the DmMyD88/tube/pelle/cactus gene cassette of the Toll pathway, wek plays a minimal role, if any, in the immune defense against Gram-positive bacteria and fungi. CONCLUSIONS: We conclude that Wek is an adaptor to link Toll and DmMyD88 and is required for efficient recruitment of DmMyD88 to Toll. Unexpectedly, wek is dispensable for innate immune response, thus revealing differences in the Toll-mediated activation of Dorsal in the embryo and Dif in the fat body of adult flies.
Galiana-Arnoux Delphine, Imler Jean-Luc
Toll-like receptors and innate antiviral immunity Journal Article
In: Tissue Antigens, vol. 67, no. 4, pp. 267–276, 2006, ISSN: 0001-2815.
Abstract | Links | BibTeX | Tags: Animals, Humans, imler, Immunity, Innate, M3i, Signal Transduction, Toll-Like Receptors, Virus Diseases
@article{galiana-arnoux_toll-like_2006,
title = {Toll-like receptors and innate antiviral immunity},
author = {Delphine Galiana-Arnoux and Jean-Luc Imler},
doi = {10.1111/j.1399-0039.2006.00583.x},
issn = {0001-2815},
year = {2006},
date = {2006-01-01},
journal = {Tissue Antigens},
volume = {67},
number = {4},
pages = {267--276},
abstract = {Viral infections are first detected by a set of innate immunity receptors that detect primary infections by pathogens, and trigger a transcriptional response. Among the induced target genes, type I interferons (IFNs) are central to the antiviral response of the host. The receptors and signaling pathways that mediate the strong induction of the synthesis of these cytokines have long remained elusive. In the past few years, Toll-like receptors (TLRs) emerged as important sensors of infections. Several TLRs participate in the recognition of virus infection, interacting in particular with viral nucleic acids. Upon activation, TLRs interact with different cytosolic adapter molecules and activate transcription factors of the nuclear factor-kappaB and IFN regulatory factor families that concur to mediate induction of IFN-alpha/beta and other inflammatory cytokines. In addition to the transmembrane TLRs, cytosolic helicases also detect viral nucleic acids, and trigger type I IFN synthesis.},
keywords = {Animals, Humans, imler, Immunity, Innate, M3i, Signal Transduction, Toll-Like Receptors, Virus Diseases},
pubstate = {published},
tppubtype = {article}
}
Viral infections are first detected by a set of innate immunity receptors that detect primary infections by pathogens, and trigger a transcriptional response. Among the induced target genes, type I interferons (IFNs) are central to the antiviral response of the host. The receptors and signaling pathways that mediate the strong induction of the synthesis of these cytokines have long remained elusive. In the past few years, Toll-like receptors (TLRs) emerged as important sensors of infections. Several TLRs participate in the recognition of virus infection, interacting in particular with viral nucleic acids. Upon activation, TLRs interact with different cytosolic adapter molecules and activate transcription factors of the nuclear factor-kappaB and IFN regulatory factor families that concur to mediate induction of IFN-alpha/beta and other inflammatory cytokines. In addition to the transmembrane TLRs, cytosolic helicases also detect viral nucleic acids, and trigger type I IFN synthesis.
2005
Dostert Catherine, Jouanguy Emmanuelle, Irving Phil, Troxler Laurent, Galiana-Arnoux Delphine, Hetru Charles, Hoffmann Jules A, Imler Jean-Luc
The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila Journal Article
In: Nature Immunology, vol. 6, no. 9, pp. 946–953, 2005, ISSN: 1529-2908.
Abstract | Links | BibTeX | Tags: Animals, bioinformatic, DNA-Binding Proteins, Genetic, Genetically Modified, hoffmann, imler, Insect Viruses, Janus Kinase 1, M3i, Male, Oligonucleotide Array Sequence Analysis, Promoter Regions, Protein-Tyrosine Kinases, Signal Transduction, STAT1 Transcription Factor, Trans-Activators
@article{dostert_jak-stat_2005,
title = {The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila},
author = {Catherine Dostert and Emmanuelle Jouanguy and Phil Irving and Laurent Troxler and Delphine Galiana-Arnoux and Charles Hetru and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1038/ni1237},
issn = {1529-2908},
year = {2005},
date = {2005-01-01},
journal = {Nature Immunology},
volume = {6},
number = {9},
pages = {946--953},
abstract = {The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate members of the transcription factor NF-kappaB family. Here we have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways and triggered a signal transducer and activator of transcription (STAT) DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third, evolutionary conserved innate immunity pathway functions in drosophila and counters viral infection.},
keywords = {Animals, bioinformatic, DNA-Binding Proteins, Genetic, Genetically Modified, hoffmann, imler, Insect Viruses, Janus Kinase 1, M3i, Male, Oligonucleotide Array Sequence Analysis, Promoter Regions, Protein-Tyrosine Kinases, Signal Transduction, STAT1 Transcription Factor, Trans-Activators},
pubstate = {published},
tppubtype = {article}
}
The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate members of the transcription factor NF-kappaB family. Here we have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways and triggered a signal transducer and activator of transcription (STAT) DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third, evolutionary conserved innate immunity pathway functions in drosophila and counters viral infection.
Weber Alexander N R, Moncrieffe Martin C, Gangloff Monique, Imler Jean-Luc, Gay Nicholas J
Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila toll pathway Journal Article
In: The Journal of Biological Chemistry, vol. 280, no. 24, pp. 22793–22799, 2005, ISSN: 0021-9258.
Abstract | Links | BibTeX | Tags: Amino Acid, Animals, Biophysical Phenomena, Biophysics, Body Patterning, Calorimetry, Cell Line, Cell Surface, Cross-Linking Reagents, Cytokines, dimerization, Electrophoresis, Humans, imler, ligands, Luciferases, M3i, Membrane Glycoproteins, Polyacrylamide Gel, Protein Binding, Protein Structure, Receptors, Recombinant Proteins, Sequence Homology, Signal Transduction, Tertiary, Time Factors, Toll-Like Receptors, Ultracentrifugation
@article{weber_ligand-receptor_2005,
title = {Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila toll pathway},
author = {Alexander N R Weber and Martin C Moncrieffe and Monique Gangloff and Jean-Luc Imler and Nicholas J Gay},
doi = {10.1074/jbc.M502074200},
issn = {0021-9258},
year = {2005},
date = {2005-01-01},
journal = {The Journal of Biological Chemistry},
volume = {280},
number = {24},
pages = {22793--22799},
abstract = {In Drosophila, the signaling pathway mediated by the Toll receptor is critical for the establishment of embryonic dorso-ventral pattern and for innate immune responses to bacterial and fungal pathogens. Toll is activated by high affinity binding of the cytokine Spätzle, a dimeric ligand of the cystine knot family. In vertebrates, a related family of Toll-like receptors play a critical role in innate immune responses. Despite the importance of this family of receptors, little is known about the biochemical events that lead to receptor activation and signaling. Here, we show that Spätzle binds to the N-terminal region of Toll and, using biophysical methods, that the binding is complex. The two binding events that cause formation of the cross-linked complex are non-equivalent: the first Toll ectodomain binds Spätzle with an affinity 3-fold higher than the second molecule suggesting that pathway activation involves negative cooperativity. We further show that the Toll ectodomains are able to form low affinity dimers in solution and that juxtamembrane sequences of Toll are critical for the activation or derepression of the pathway. These results, taken together, suggest a mechanism of signal transduction that requires both ligand-receptor and receptor-receptor interactions.},
keywords = {Amino Acid, Animals, Biophysical Phenomena, Biophysics, Body Patterning, Calorimetry, Cell Line, Cell Surface, Cross-Linking Reagents, Cytokines, dimerization, Electrophoresis, Humans, imler, ligands, Luciferases, M3i, Membrane Glycoproteins, Polyacrylamide Gel, Protein Binding, Protein Structure, Receptors, Recombinant Proteins, Sequence Homology, Signal Transduction, Tertiary, Time Factors, Toll-Like Receptors, Ultracentrifugation},
pubstate = {published},
tppubtype = {article}
}
In Drosophila, the signaling pathway mediated by the Toll receptor is critical for the establishment of embryonic dorso-ventral pattern and for innate immune responses to bacterial and fungal pathogens. Toll is activated by high affinity binding of the cytokine Spätzle, a dimeric ligand of the cystine knot family. In vertebrates, a related family of Toll-like receptors play a critical role in innate immune responses. Despite the importance of this family of receptors, little is known about the biochemical events that lead to receptor activation and signaling. Here, we show that Spätzle binds to the N-terminal region of Toll and, using biophysical methods, that the binding is complex. The two binding events that cause formation of the cross-linked complex are non-equivalent: the first Toll ectodomain binds Spätzle with an affinity 3-fold higher than the second molecule suggesting that pathway activation involves negative cooperativity. We further show that the Toll ectodomains are able to form low affinity dimers in solution and that juxtamembrane sequences of Toll are critical for the activation or derepression of the pathway. These results, taken together, suggest a mechanism of signal transduction that requires both ligand-receptor and receptor-receptor interactions.
Imler Jean-Luc, Bulet Philippe
Antimicrobial peptides in Drosophila: structures, activities and gene regulation Journal Article
In: Chemical Immunology and Allergy, vol. 86, pp. 1–21, 2005, ISSN: 1660-2242.
Abstract | Links | BibTeX | Tags: Animals, Antimicrobial Cationic Peptides, Defensins, Gene Expression Regulation, Genes, Glycopeptides, imler, Immunity, Innate, Insect, Insect Proteins, M3i, Molecular Structure, Signal Transduction
@article{imler_antimicrobial_2005,
title = {Antimicrobial peptides in Drosophila: structures, activities and gene regulation},
author = {Jean-Luc Imler and Philippe Bulet},
doi = {10.1159/000086648},
issn = {1660-2242},
year = {2005},
date = {2005-01-01},
journal = {Chemical Immunology and Allergy},
volume = {86},
pages = {1--21},
abstract = {The production of antimicrobial peptides (AMPs) is an important aspect of host-defence in multicellular organisms. Biochemical analysis of the hemolymph of the fruit-fly Drosophila melanogaster and other Diptera has led to the discovery of eight classes of AMPs. These peptides can be grouped into three families based on their main biological targets, gram-positive bacteria (defensin), gram-negative bacteria (cecropins, drosocin, attacins, diptericin, MPAC), or fungi (drosomycin, metchnikowin). Drosophila AMPs are synthesized by the fat body in response to infection, and secreted into the blood. Most of them can also be induced in surface epithelia in a tissue-specific manner. Finally, some of them are constitutively expressed in defined tissues, such as the salivary glands or the reproductive tract. We review here the structures and activities of these AMPs, as well as the signalling cascades, which lead to their induction upon detection of infectious non-self.},
keywords = {Animals, Antimicrobial Cationic Peptides, Defensins, Gene Expression Regulation, Genes, Glycopeptides, imler, Immunity, Innate, Insect, Insect Proteins, M3i, Molecular Structure, Signal Transduction},
pubstate = {published},
tppubtype = {article}
}
The production of antimicrobial peptides (AMPs) is an important aspect of host-defence in multicellular organisms. Biochemical analysis of the hemolymph of the fruit-fly Drosophila melanogaster and other Diptera has led to the discovery of eight classes of AMPs. These peptides can be grouped into three families based on their main biological targets, gram-positive bacteria (defensin), gram-negative bacteria (cecropins, drosocin, attacins, diptericin, MPAC), or fungi (drosomycin, metchnikowin). Drosophila AMPs are synthesized by the fat body in response to infection, and secreted into the blood. Most of them can also be induced in surface epithelia in a tissue-specific manner. Finally, some of them are constitutively expressed in defined tissues, such as the salivary glands or the reproductive tract. We review here the structures and activities of these AMPs, as well as the signalling cascades, which lead to their induction upon detection of infectious non-self.
2004
Ferrandon Dominique, Imler Jean-Luc, Hoffmann Jules A
Sensing infection in Drosophila: Toll and beyond Journal Article
In: Semin Immunol, vol. 16, pp. 43–53, 2004, ISSN: 1044-5323.
Abstract | BibTeX | Tags: Animals, Carrier Proteins/chemistry/immunology/physiology, Cell Surface/immunology/*physiology, Drosophila Proteins/chemistry/immunology/*physiology, Drosophila/genetics/*immunology/microbiology, ferrandon, Fungi/immunology, Gene Expression Regulation, Gram-Negative Bacterial Infections/immunology, Gram-Positive Bacterial Infections/immunology, hoffmann, imler, Immunological, Insect Proteins/chemistry/immunology/physiology, M3i, Models, Non-U.S. Gov't, Receptors, Signal Transduction/immunology/physiology, Support
@article{ferrandon_sensing_2004b,
title = {Sensing infection in Drosophila: Toll and beyond},
author = {Dominique Ferrandon and Jean-Luc Imler and Jules A Hoffmann},
issn = {1044-5323},
year = {2004},
date = {2004-01-01},
journal = {Semin Immunol},
volume = {16},
pages = {43--53},
abstract = {Drosophila has evolved a potent immune system that is somewhat adapted to the nature of infections through the selective activation of either one of two NF-kappa B-like signalling pathways, the Toll and IMD (Immune deficiency) pathways. In contrast to the mammalian system, the Toll receptor does not act as a pattern recognition receptor (PRR) but as a cytokine receptor. The sensing of microbial infections is achieved by at least four PRRs that belong to two distinct families: the peptidoglycan recognition proteins (PGRPs) and the Gram-negative binding proteins (GNBPs)/beta-glucan recognition proteins (beta GRPs).},
keywords = {Animals, Carrier Proteins/chemistry/immunology/physiology, Cell Surface/immunology/*physiology, Drosophila Proteins/chemistry/immunology/*physiology, Drosophila/genetics/*immunology/microbiology, ferrandon, Fungi/immunology, Gene Expression Regulation, Gram-Negative Bacterial Infections/immunology, Gram-Positive Bacterial Infections/immunology, hoffmann, imler, Immunological, Insect Proteins/chemistry/immunology/physiology, M3i, Models, Non-U.S. Gov't, Receptors, Signal Transduction/immunology/physiology, Support},
pubstate = {published},
tppubtype = {article}
}
Drosophila has evolved a potent immune system that is somewhat adapted to the nature of infections through the selective activation of either one of two NF-kappa B-like signalling pathways, the Toll and IMD (Immune deficiency) pathways. In contrast to the mammalian system, the Toll receptor does not act as a pattern recognition receptor (PRR) but as a cytokine receptor. The sensing of microbial infections is achieved by at least four PRRs that belong to two distinct families: the peptidoglycan recognition proteins (PGRPs) and the Gram-negative binding proteins (GNBPs)/beta-glucan recognition proteins (beta GRPs).
Imler Jean-Luc, Zheng Liangbiao
Biology of Toll receptors: lessons from insects and mammals Journal Article
In: Journal of Leukocyte Biology, vol. 75, no. 1, pp. 18–26, 2004, ISSN: 0741-5400.
Abstract | Links | BibTeX | Tags: Animals, Anopheles, Cell Surface, Humans, imler, M3i, Membrane Glycoproteins, Mice, Phylogeny, Plant Physiological Phenomena, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors
@article{imler_biology_2004,
title = {Biology of Toll receptors: lessons from insects and mammals},
author = {Jean-Luc Imler and Liangbiao Zheng},
doi = {10.1189/jlb.0403160},
issn = {0741-5400},
year = {2004},
date = {2004-01-01},
journal = {Journal of Leukocyte Biology},
volume = {75},
number = {1},
pages = {18--26},
abstract = {Toll receptors are type I transmembrane proteins that play important roles in development and immunity in animals. Comparison of the genomes of mouse and human on one side and of the fruitfly Drosophila and the mosquito Anopheles (two dipteran insects) on the other, revealed that the four species possess a similar number of Toll receptors (approximately 10). However, phylogenetic analyses indicate that the families of Toll receptors expanded independently in insects and mammals. We review recent results on these receptors, which point to differences in the activation and signaling between Tolls in insects and Toll-like receptors (TLRs) in mammals. Whereas mammalian TLRs appear to be solely dedicated to host-defense, insect Tolls may be predominantly linked to other functions, probably developmental.},
keywords = {Animals, Anopheles, Cell Surface, Humans, imler, M3i, Membrane Glycoproteins, Mice, Phylogeny, Plant Physiological Phenomena, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Toll receptors are type I transmembrane proteins that play important roles in development and immunity in animals. Comparison of the genomes of mouse and human on one side and of the fruitfly Drosophila and the mosquito Anopheles (two dipteran insects) on the other, revealed that the four species possess a similar number of Toll receptors (approximately 10). However, phylogenetic analyses indicate that the families of Toll receptors expanded independently in insects and mammals. We review recent results on these receptors, which point to differences in the activation and signaling between Tolls in insects and Toll-like receptors (TLRs) in mammals. Whereas mammalian TLRs appear to be solely dedicated to host-defense, insect Tolls may be predominantly linked to other functions, probably developmental.
Imler Jean-Luc, Ferrandon Dominique, Royet Julien, Reichhart Jean-Marc, Hetru Charles, Hoffmann Jules A
Toll-dependent and Toll-independent immune responses in Drosophila Journal Article
In: Journal of Endotoxin Research, vol. 10, no. 4, pp. 241–246, 2004, ISSN: 0968-0519.
Abstract | Links | BibTeX | Tags: Acute-Phase Proteins, Animals, Blood Proteins, Cell Surface, ferrandon, hoffmann, imler, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors, Up-Regulation
@article{imler_toll-dependent_2004,
title = {Toll-dependent and Toll-independent immune responses in Drosophila},
author = {Jean-Luc Imler and Dominique Ferrandon and Julien Royet and Jean-Marc Reichhart and Charles Hetru and Jules A Hoffmann},
doi = {10.1179/096805104225005887},
issn = {0968-0519},
year = {2004},
date = {2004-01-01},
journal = {Journal of Endotoxin Research},
volume = {10},
number = {4},
pages = {241--246},
abstract = {The multifaceted response of the fruitfly Drosophila melanogaster to infection by a wide range of microbes is complex and remarkably efficient. Its most prominent aspect is the immune-inducible expression of a set of potent antimicrobial peptides. Genetic analysis of the regulation of the genes encoding these peptides has led to the identification of the receptor Toll as an essential component of the fly's host defense system. In addition, these studies have revealed that the response to Gram-negative bacterial infections involves Toll-independent mechanisms, and that the sensing of infection involves two structurally distinct sets of molecules--the PGRPs and the GNBPs/betaGRPs.},
keywords = {Acute-Phase Proteins, Animals, Blood Proteins, Cell Surface, ferrandon, hoffmann, imler, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors, Up-Regulation},
pubstate = {published},
tppubtype = {article}
}
The multifaceted response of the fruitfly Drosophila melanogaster to infection by a wide range of microbes is complex and remarkably efficient. Its most prominent aspect is the immune-inducible expression of a set of potent antimicrobial peptides. Genetic analysis of the regulation of the genes encoding these peptides has led to the identification of the receptor Toll as an essential component of the fly's host defense system. In addition, these studies have revealed that the response to Gram-negative bacterial infections involves Toll-independent mechanisms, and that the sensing of infection involves two structurally distinct sets of molecules--the PGRPs and the GNBPs/betaGRPs.
2003
Weber Alexander N R, Tauszig-Delamasure Servane, Hoffmann Jules A, Lelièvre Eric, Gascan Hugues, Ray Keith P, Morse Mary A, Imler Jean-Luc, Gay Nicholas J
Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling Journal Article
In: Nature Immunology, vol. 4, no. 8, pp. 794–800, 2003, ISSN: 1529-2908.
Abstract | Links | BibTeX | Tags: Animals, Cell Surface, hoffmann, imler, Insect Proteins, M3i, Protein Binding, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors
@article{weber_binding_2003,
title = {Binding of the Drosophila cytokine Spätzle to Toll is direct and establishes signaling},
author = {Alexander N R Weber and Servane Tauszig-Delamasure and Jules A Hoffmann and Eric Lelièvre and Hugues Gascan and Keith P Ray and Mary A Morse and Jean-Luc Imler and Nicholas J Gay},
doi = {10.1038/ni955},
issn = {1529-2908},
year = {2003},
date = {2003-08-01},
journal = {Nature Immunology},
volume = {4},
number = {8},
pages = {794--800},
abstract = {The extracellular protein Spätzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Spätzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Spätzle triggers a Toll-dependent immune response after injection into the hemolymph of flies. Spätzle specifically bound to Drosophila cells and to Cos-7 cells expressing Toll. Furthermore, in vitro experiments showed that the mature form of Spätzle bound to the Toll ectodomain with high affinity and with a stoichiometry of one Spätzle dimer to two receptors. The Spätzle pro-protein was inactive in all these assays, indicating that the pro-domain sequence, which is natively unstructured, acts to prevent interaction of the cytokine and its receptor Toll. These results show that, in contrast to the human Toll-like receptors, Drosophila Toll requires only an endogenous protein ligand for activation and signaling.},
keywords = {Animals, Cell Surface, hoffmann, imler, Insect Proteins, M3i, Protein Binding, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
The extracellular protein Spätzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Spätzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Spätzle triggers a Toll-dependent immune response after injection into the hemolymph of flies. Spätzle specifically bound to Drosophila cells and to Cos-7 cells expressing Toll. Furthermore, in vitro experiments showed that the mature form of Spätzle bound to the Toll ectodomain with high affinity and with a stoichiometry of one Spätzle dimer to two receptors. The Spätzle pro-protein was inactive in all these assays, indicating that the pro-domain sequence, which is natively unstructured, acts to prevent interaction of the cytokine and its receptor Toll. These results show that, in contrast to the human Toll-like receptors, Drosophila Toll requires only an endogenous protein ligand for activation and signaling.
Bilak Hana, Tauszig-Delamasure S, Imler Jean-Luc
Toll and Toll-like receptors in Drosophila Journal Article
In: Biochemical Society Transactions, vol. 31, no. Pt 3, pp. 648–651, 2003, ISSN: 0300-5127.
Abstract | Links | BibTeX | Tags: Animals, Biological Evolution, Cell Surface, Fungi, Genome, Gram-Negative Bacteria, Gram-Positive Bacteria, imler, M3i, Membrane Glycoproteins, Receptors, Toll-Like Receptor 5, Toll-Like Receptors
@article{bilak_toll_2003,
title = {Toll and Toll-like receptors in Drosophila},
author = {Hana Bilak and S Tauszig-Delamasure and Jean-Luc Imler},
doi = {10.1042/},
issn = {0300-5127},
year = {2003},
date = {2003-06-01},
journal = {Biochemical Society Transactions},
volume = {31},
number = {Pt 3},
pages = {648--651},
abstract = {The Drosophila Toll receptor controls the immune response to Gram-positive bacteria and fungi by activating a signalling pathway partially conserved throughout evolution. The Drosophila genome encodes eight additional Toll-related receptors, most of which appear to carry out developmental rather than immune functions. One exception may be Toll-9, which shares structural and functional similarities with mammalian TLRs.},
keywords = {Animals, Biological Evolution, Cell Surface, Fungi, Genome, Gram-Negative Bacteria, Gram-Positive Bacteria, imler, M3i, Membrane Glycoproteins, Receptors, Toll-Like Receptor 5, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
The Drosophila Toll receptor controls the immune response to Gram-positive bacteria and fungi by activating a signalling pathway partially conserved throughout evolution. The Drosophila genome encodes eight additional Toll-related receptors, most of which appear to carry out developmental rather than immune functions. One exception may be Toll-9, which shares structural and functional similarities with mammalian TLRs.
Luna C, Hoa N T, Zhang J, Kanzok S M, Brown S E, Imler Jean-Luc, Knudson D L, Zheng L
Characterization of three Toll-like genes from mosquito Aedes aegypti Journal Article
In: Insect Molecular Biology, vol. 12, no. 1, pp. 67–74, 2003, ISSN: 0962-1075.
Abstract | BibTeX | Tags: Aedes, Animals, Base Sequence, Cell Surface, Chimera, Cloning, Developmental, Female, Gene Expression Regulation, Genetic, imler, Insect Proteins, M3i, Male, messenger, Models, Molecular, Mutagenesis, Promoter Regions, Receptors, Reverse Transcriptase Polymerase Chain Reaction, RNA, Sequence Alignment, Signal Transduction, Site-Directed, Transfection
@article{luna_characterization_2003,
title = {Characterization of three Toll-like genes from mosquito Aedes aegypti},
author = {C Luna and N T Hoa and J Zhang and S M Kanzok and S E Brown and Jean-Luc Imler and D L Knudson and L Zheng},
issn = {0962-1075},
year = {2003},
date = {2003-02-01},
journal = {Insect Molecular Biology},
volume = {12},
number = {1},
pages = {67--74},
abstract = {Three Toll-related genes (AeToll1A, AeToll1B and AeToll5) were cloned and characterized from the yellow fever vector mosquito, Aedes aegypti. All three genes exhibited high levels of amino acid sequence similarity with Drosophila melanogaster (Dm)Toll1 and DmTehao (Toll5). AeToll1A and AeToll1B are 1124 and 1076 amino acid residues long, respectively. Both contain a carboxyl extension downstream of the Toll/interleukin-1 receptor (TIR) domain. AeToll5 is 1007 residues long and, like DmTehao, lacks the carboxyl terminal extension. Expression of these three genes was examined throughout development and after immune challenge. Both AeToll1A and AeToll5, like their Drosophila counterparts, activate transcription of drosomycin promoter in both Aedes and Drosophila cell lines. Deletion of the carboxyl extension of AeToll1A did not result in a further elevated level of the antifungal response. The intracellular signalling process appears to be species specific based on two observations. (1) DmToll is completely inactive in an Aedes cell line, suggesting a higher specificity requirement for DmToll in the intracellular signalling process. (2) Only one of three amino acid residues essential for DmToll function is required for AeToll1A function.},
keywords = {Aedes, Animals, Base Sequence, Cell Surface, Chimera, Cloning, Developmental, Female, Gene Expression Regulation, Genetic, imler, Insect Proteins, M3i, Male, messenger, Models, Molecular, Mutagenesis, Promoter Regions, Receptors, Reverse Transcriptase Polymerase Chain Reaction, RNA, Sequence Alignment, Signal Transduction, Site-Directed, Transfection},
pubstate = {published},
tppubtype = {article}
}
Three Toll-related genes (AeToll1A, AeToll1B and AeToll5) were cloned and characterized from the yellow fever vector mosquito, Aedes aegypti. All three genes exhibited high levels of amino acid sequence similarity with Drosophila melanogaster (Dm)Toll1 and DmTehao (Toll5). AeToll1A and AeToll1B are 1124 and 1076 amino acid residues long, respectively. Both contain a carboxyl extension downstream of the Toll/interleukin-1 receptor (TIR) domain. AeToll5 is 1007 residues long and, like DmTehao, lacks the carboxyl terminal extension. Expression of these three genes was examined throughout development and after immune challenge. Both AeToll1A and AeToll5, like their Drosophila counterparts, activate transcription of drosomycin promoter in both Aedes and Drosophila cell lines. Deletion of the carboxyl extension of AeToll1A did not result in a further elevated level of the antifungal response. The intracellular signalling process appears to be species specific based on two observations. (1) DmToll is completely inactive in an Aedes cell line, suggesting a higher specificity requirement for DmToll in the intracellular signalling process. (2) Only one of three amino acid residues essential for DmToll function is required for AeToll1A function.
Imler Jean-Luc, Hoffmann Jules A
Toll signaling: the TIReless quest for specificity Journal Article
In: Nature Immunology, vol. 4, no. 2, pp. 105–106, 2003, ISSN: 1529-2908.
Links | BibTeX | Tags: Animals, Cell Surface, Dendritic Cells, hoffmann, Humans, imler, Immunological, Interferon-beta, M3i, Membrane Glycoproteins, Mice, Models, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors
@article{imler_toll_2003,
title = {Toll signaling: the TIReless quest for specificity},
author = {Jean-Luc Imler and Jules A Hoffmann},
doi = {10.1038/ni0203-105},
issn = {1529-2908},
year = {2003},
date = {2003-02-01},
journal = {Nature Immunology},
volume = {4},
number = {2},
pages = {105--106},
keywords = {Animals, Cell Surface, Dendritic Cells, hoffmann, Humans, imler, Immunological, Interferon-beta, M3i, Membrane Glycoproteins, Mice, Models, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Kambris Zakaria, Bilak Hana, D'Alessandro Rosalba, Belvin Marcia, Imler Jean-Luc, Capovilla Maria
DmMyD88 controls dorsoventral patterning of the Drosophila embryo Journal Article
In: EMBO reports, vol. 4, no. 1, pp. 64–69, 2003, ISSN: 1469-221X.
Abstract | Links | BibTeX | Tags: Adaptor Proteins, Alleles, Animals, Antigens, Base Sequence, Cell Surface, Complementary, Developmental, Differentiation, DNA, DNA Transposable Elements, Egg Proteins, Embryo, Exons, Female, Gene Expression Regulation, Genetically Modified, Genotype, imler, Immunity, Immunologic, Innate, Insertional, M3i, Male, messenger, Morphogenesis, Mutagenesis, Myeloid Differentiation Factor 88, Nonmammalian, Oocytes, Protein Biosynthesis, Protein Structure, Receptors, Reverse Transcriptase Polymerase Chain Reaction, RNA, Signal Transducing, Tertiary, Toll-Like Receptors, Zygote
@article{kambris_dmmyd88_2003,
title = {DmMyD88 controls dorsoventral patterning of the Drosophila embryo},
author = {Zakaria Kambris and Hana Bilak and Rosalba D'Alessandro and Marcia Belvin and Jean-Luc Imler and Maria Capovilla},
doi = {10.1038/sj.embor.embor714},
issn = {1469-221X},
year = {2003},
date = {2003-01-01},
journal = {EMBO reports},
volume = {4},
number = {1},
pages = {64--69},
abstract = {MyD88 is an adapter protein in the signal transduction pathway mediated by interleukin-1 (IL-1) and Toll-like receptors. A Drosophila homologue of MyD88 (DmMyD88) was recently shown to be required for the Toll-mediated immune response. In Drosophila, the Toll pathway was originally characterized for its role in the dorsoventral patterning of the embryo. We found that, like Toll, DmMyD88 messenger RNA is maternally supplied to the embryo. Here we report the identification of a new mutant allele of DmMyD88, which generates a protein lacking the carboxy-terminal extension, normally located downstream of the Toll/IL-1 receptor domain. Homozygous mutant female flies lay dorsalized embryos that are rescued by expression of a transgenic DmMyD88 complementary DNA. The DmMyD88 mutation blocks the ventralizing activity of a gain-of-function Toll mutation. These results show that DmMyD88 encodes an essential component of the Toll pathway in dorsoventral pattern formation.},
keywords = {Adaptor Proteins, Alleles, Animals, Antigens, Base Sequence, Cell Surface, Complementary, Developmental, Differentiation, DNA, DNA Transposable Elements, Egg Proteins, Embryo, Exons, Female, Gene Expression Regulation, Genetically Modified, Genotype, imler, Immunity, Immunologic, Innate, Insertional, M3i, Male, messenger, Morphogenesis, Mutagenesis, Myeloid Differentiation Factor 88, Nonmammalian, Oocytes, Protein Biosynthesis, Protein Structure, Receptors, Reverse Transcriptase Polymerase Chain Reaction, RNA, Signal Transducing, Tertiary, Toll-Like Receptors, Zygote},
pubstate = {published},
tppubtype = {article}
}
MyD88 is an adapter protein in the signal transduction pathway mediated by interleukin-1 (IL-1) and Toll-like receptors. A Drosophila homologue of MyD88 (DmMyD88) was recently shown to be required for the Toll-mediated immune response. In Drosophila, the Toll pathway was originally characterized for its role in the dorsoventral patterning of the embryo. We found that, like Toll, DmMyD88 messenger RNA is maternally supplied to the embryo. Here we report the identification of a new mutant allele of DmMyD88, which generates a protein lacking the carboxy-terminal extension, normally located downstream of the Toll/IL-1 receptor domain. Homozygous mutant female flies lay dorsalized embryos that are rescued by expression of a transgenic DmMyD88 complementary DNA. The DmMyD88 mutation blocks the ventralizing activity of a gain-of-function Toll mutation. These results show that DmMyD88 encodes an essential component of the Toll pathway in dorsoventral pattern formation.
Sabatier Laurence, Jouanguy Emmanuelle, Dostert Catherine, Zachary Daniel, Dimarcq Jean-Luc, Bulet Philippe, Imler Jean-Luc
Pherokine-2 and -3 Journal Article
In: European journal of biochemistry / FEBS, vol. 270, no. 16, pp. 3398–3407, 2003, ISSN: 0014-2956.
Abstract | BibTeX | Tags: Animals, Antibody Formation, Base Sequence, Hemolymph, imler, M3i, Mass, Matrix-Assisted Laser Desorption-Ionization, Spectrometry
@article{sabatier_pherokine-2_2003,
title = {Pherokine-2 and -3},
author = {Laurence Sabatier and Emmanuelle Jouanguy and Catherine Dostert and Daniel Zachary and Jean-Luc Dimarcq and Philippe Bulet and Jean-Luc Imler},
issn = {0014-2956},
year = {2003},
date = {2003-01-01},
journal = {European journal of biochemistry / FEBS},
volume = {270},
number = {16},
pages = {3398--3407},
abstract = {Drosophila is a powerful model system to study the regulatory and effector mechanisms of innate immunity. To identify molecules induced in the course of viral infection in this insect, we have developed a model based on intrathoracic injection of the picorna-like Drosophila C virus (DCV). We have used MALDI-TOF mass spectrometry to compare the hemolymph of DCV infected flies and control flies. By contrast with the strong humoral response triggered by injection of bacteria or fungal spores, we have identified only one molecule induced in the hemolymph of virus infected flies. This molecule, pherokine-2 (Phk-2), is related to OS-D/A10 (Phk-1), which was previously characterized as a putative odor/pheromone binding protein specifically expressed in antennae. The virus-induced molecule is also similar to the product of the gene CG9358 (Phk-3), which is induced by septic injury. Both Phk-2 and Phk-3 are strongly expressed during metamorphosis, suggesting that they may participate in tissue-remodeling.},
keywords = {Animals, Antibody Formation, Base Sequence, Hemolymph, imler, M3i, Mass, Matrix-Assisted Laser Desorption-Ionization, Spectrometry},
pubstate = {published},
tppubtype = {article}
}
Drosophila is a powerful model system to study the regulatory and effector mechanisms of innate immunity. To identify molecules induced in the course of viral infection in this insect, we have developed a model based on intrathoracic injection of the picorna-like Drosophila C virus (DCV). We have used MALDI-TOF mass spectrometry to compare the hemolymph of DCV infected flies and control flies. By contrast with the strong humoral response triggered by injection of bacteria or fungal spores, we have identified only one molecule induced in the hemolymph of virus infected flies. This molecule, pherokine-2 (Phk-2), is related to OS-D/A10 (Phk-1), which was previously characterized as a putative odor/pheromone binding protein specifically expressed in antennae. The virus-induced molecule is also similar to the product of the gene CG9358 (Phk-3), which is induced by septic injury. Both Phk-2 and Phk-3 are strongly expressed during metamorphosis, suggesting that they may participate in tissue-remodeling.
2002
Kambris Zakaria, Hoffmann Jules A, Imler Jean-Luc, Capovilla Maria
Tissue and stage-specific expression of the Tolls in Drosophila embryos Journal Article
In: Gene expression patterns: GEP, vol. 2, no. 3-4, pp. 311–317, 2002, ISSN: 1567-133X.
Abstract | BibTeX | Tags: Animals, Blotting, Cell Surface, Gene Expression Profiling, hoffmann, imler, Larva, M3i, Multigene Family, Northern, Receptors, Toll-Like Receptors
@article{kambris_tissue_2002,
title = {Tissue and stage-specific expression of the Tolls in Drosophila embryos},
author = {Zakaria Kambris and Jules A Hoffmann and Jean-Luc Imler and Maria Capovilla},
issn = {1567-133X},
year = {2002},
date = {2002-12-01},
journal = {Gene expression patterns: GEP},
volume = {2},
number = {3-4},
pages = {311--317},
abstract = {The Drosophila transmembrane receptor Toll plays a key role in specifying the dorsoventral axis of the embryo. At later stages of development, it controls the immune response of the fly to fungal and Gram-positive bacterial infections. The Drosophila genome has a total of nine Toll-like genes, including the previously characterized Toll (Toll-1) and 18-wheeler (Toll-2). Here we describe the embryonic expression patterns of the seven Toll-like genes Toll-3 through Toll-9. We find that these genes have distinct expression domains and that their expression is dynamically changing throughout embryonic development. This complex and tissue-specific regulation of Toll-like gene expression strongly suggests a role in embryonic development for most Drosophila Tolls. The evolving picture on the Toll family members in Drosophila contrasts with that of mammalian Toll-like receptors, which are predominantly expressed in immune responsive cells where their activation occurs via microbial structural determinants.},
keywords = {Animals, Blotting, Cell Surface, Gene Expression Profiling, hoffmann, imler, Larva, M3i, Multigene Family, Northern, Receptors, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
The Drosophila transmembrane receptor Toll plays a key role in specifying the dorsoventral axis of the embryo. At later stages of development, it controls the immune response of the fly to fungal and Gram-positive bacterial infections. The Drosophila genome has a total of nine Toll-like genes, including the previously characterized Toll (Toll-1) and 18-wheeler (Toll-2). Here we describe the embryonic expression patterns of the seven Toll-like genes Toll-3 through Toll-9. We find that these genes have distinct expression domains and that their expression is dynamically changing throughout embryonic development. This complex and tissue-specific regulation of Toll-like gene expression strongly suggests a role in embryonic development for most Drosophila Tolls. The evolving picture on the Toll family members in Drosophila contrasts with that of mammalian Toll-like receptors, which are predominantly expressed in immune responsive cells where their activation occurs via microbial structural determinants.
Reichhart Jean-Marc, Ligoxygakis Petros, Naitza Silvia, Woerfel Gertrud, Imler Jean-Luc, Gubb David
Splice-activated UAS hairpin vector gives complete RNAi knockout of single or double target transcripts in Drosophila melanogaster Journal Article
In: Genesis (New York, N.Y.: 2000), vol. 34, no. 1-2, pp. 160–164, 2002, ISSN: 1526-954X.
Links | BibTeX | Tags: Animals, DNA Transposable Elements, DNA-Binding Proteins, Enhancer Elements, Genetic, Genetic Vectors, Genetically Modified, imler, M3i, reichhart, Saccharomyces cerevisiae Proteins, Transcription Factors
@article{reichhart_splice-activated_2002,
title = {Splice-activated UAS hairpin vector gives complete RNAi knockout of single or double target transcripts in Drosophila melanogaster},
author = {Jean-Marc Reichhart and Petros Ligoxygakis and Silvia Naitza and Gertrud Woerfel and Jean-Luc Imler and David Gubb},
doi = {10.1002/gene.10122},
issn = {1526-954X},
year = {2002},
date = {2002-01-01},
journal = {Genesis (New York, N.Y.: 2000)},
volume = {34},
number = {1-2},
pages = {160--164},
keywords = {Animals, DNA Transposable Elements, DNA-Binding Proteins, Enhancer Elements, Genetic, Genetic Vectors, Genetically Modified, imler, M3i, reichhart, Saccharomyces cerevisiae Proteins, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
Tauszig-Delamasure Servane, Bilak Hana, Capovilla Maria, Hoffmann Jules A, Imler Jean-Luc
Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections Journal Article
In: Nature Immunology, vol. 3, no. 1, pp. 91–97, 2002, ISSN: 1529-2908.
Abstract | Links | BibTeX | Tags: Adaptor Proteins, Amino Acid, Animals, Antigens, Antimicrobial Cationic Peptides, Cell Surface, Chromosome Mapping, Differentiation, Disease Susceptibility, Enterococcus faecalis, Epistasis, Escherichia coli, Female, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Gram-Negative Bacteria, hoffmann, Hypocreales, imler, Immunologic, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Myeloid Differentiation Factor 88, Protein Structure, Protein-Serine-Threonine Kinases, Receptors, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Signal Transducing, Tertiary, Toll-Like Receptors, Transfection
@article{tauszig-delamasure_drosophila_2002,
title = {Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections},
author = {Servane Tauszig-Delamasure and Hana Bilak and Maria Capovilla and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1038/ni747},
issn = {1529-2908},
year = {2002},
date = {2002-01-01},
journal = {Nature Immunology},
volume = {3},
number = {1},
pages = {91--97},
abstract = {We report here the identification and functional characterization of DmMyD88, a gene encoding the Drosophila homolog of mammalian MyD88. DmMyD88 combines a Toll-IL-1R homology (TIR) domain and a death domain. Overexpression of DmMyD88 was sufficient to induce expression of the antifungal peptide Drosomycin, and induction of Drosomycin was markedly reduced in DmMyD88-mutant flies. DmMyD88 interacted with Toll through its TIR domain and required the death domain proteins Tube and Pelle to activate expression of Drs, which encodes Drosomycin. DmMyD88-mutant flies were highly susceptible to infection by fungi and Gram-positive bacteria, but resisted Gram-negative bacterial infection much as did wild-type flies. Phenotypic comparison of DmMyD88-mutant flies and MyD88-deficient mice showed essential differences in the control of Gram-negative infection in insects and mammals.},
keywords = {Adaptor Proteins, Amino Acid, Animals, Antigens, Antimicrobial Cationic Peptides, Cell Surface, Chromosome Mapping, Differentiation, Disease Susceptibility, Enterococcus faecalis, Epistasis, Escherichia coli, Female, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Gram-Negative Bacteria, hoffmann, Hypocreales, imler, Immunologic, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Myeloid Differentiation Factor 88, Protein Structure, Protein-Serine-Threonine Kinases, Receptors, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Signal Transducing, Tertiary, Toll-Like Receptors, Transfection},
pubstate = {published},
tppubtype = {article}
}
We report here the identification and functional characterization of DmMyD88, a gene encoding the Drosophila homolog of mammalian MyD88. DmMyD88 combines a Toll-IL-1R homology (TIR) domain and a death domain. Overexpression of DmMyD88 was sufficient to induce expression of the antifungal peptide Drosomycin, and induction of Drosomycin was markedly reduced in DmMyD88-mutant flies. DmMyD88 interacted with Toll through its TIR domain and required the death domain proteins Tube and Pelle to activate expression of Drs, which encodes Drosomycin. DmMyD88-mutant flies were highly susceptible to infection by fungi and Gram-positive bacteria, but resisted Gram-negative bacterial infection much as did wild-type flies. Phenotypic comparison of DmMyD88-mutant flies and MyD88-deficient mice showed essential differences in the control of Gram-negative infection in insects and mammals.
Imler Jean-Luc, Hoffmann Jules A
Toll receptors in Drosophila: a family of molecules regulating development and immunity Journal Article
In: Current Topics in Microbiology and Immunology, vol. 270, pp. 63–79, 2002, ISSN: 0070-217X.
Abstract | BibTeX | Tags: Animals, Cell Surface, Genetic, Gram-Negative Bacteria, hoffmann, imler, M3i, Receptors, Signal Transduction, Toll-Like Receptors, Transcription
@article{imler_toll_2002,
title = {Toll receptors in Drosophila: a family of molecules regulating development and immunity},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {0070-217X},
year = {2002},
date = {2002-01-01},
journal = {Current Topics in Microbiology and Immunology},
volume = {270},
pages = {63--79},
abstract = {In recent years, Toll-like receptors (TLRs) have emerged as key receptors which detect microbes and initiate an inflammatory response. The Toll receptor was originally identified and characterized 14 years ago for its role in the embryonic development of the fruit-fly Drosophila melanogaster. Subsequently, it was also shown to be an essential component of the signaling pathway mediating the anti-fungal host defense in this model organism. New factors involved in the activation of the Toll receptor or in intracytoplasmic signaling during the immune response in Drosophila have recently been identified. The existence of significant functional differences between mammalian TLRs and Drosophila Toll receptors is also becoming apparent.},
keywords = {Animals, Cell Surface, Genetic, Gram-Negative Bacteria, hoffmann, imler, M3i, Receptors, Signal Transduction, Toll-Like Receptors, Transcription},
pubstate = {published},
tppubtype = {article}
}
In recent years, Toll-like receptors (TLRs) have emerged as key receptors which detect microbes and initiate an inflammatory response. The Toll receptor was originally identified and characterized 14 years ago for its role in the embryonic development of the fruit-fly Drosophila melanogaster. Subsequently, it was also shown to be an essential component of the signaling pathway mediating the anti-fungal host defense in this model organism. New factors involved in the activation of the Toll receptor or in intracytoplasmic signaling during the immune response in Drosophila have recently been identified. The existence of significant functional differences between mammalian TLRs and Drosophila Toll receptors is also becoming apparent.
2001
Boulanger Nathalie, Ehret-Sabatier Laurence, Brun R, Zachary Daniel, Bulet Philippe, Imler Jean-Luc
Immune response of Drosophila melanogaster to infection with the flagellate parasite Crithidia spp Journal Article
In: Insect Biochemistry and Molecular Biology, vol. 31, no. 2, pp. 129–137, 2001, ISSN: 0965-1748.
Abstract | BibTeX | Tags: Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Crithidia, Defensins, Gene Expression, Glycopeptides, Hemocytes, imler, Insect Proteins, M3i, Phagocytosis
@article{boulanger_immune_2001,
title = {Immune response of Drosophila melanogaster to infection with the flagellate parasite Crithidia spp},
author = {Nathalie Boulanger and Laurence Ehret-Sabatier and R Brun and Daniel Zachary and Philippe Bulet and Jean-Luc Imler},
issn = {0965-1748},
year = {2001},
date = {2001-02-01},
journal = {Insect Biochemistry and Molecular Biology},
volume = {31},
number = {2},
pages = {129--137},
abstract = {Insects are able to recognize invading microorganisms and to mount an immune response to bacterial and fungal infections. Recently, the fruitfly Drosophila melanogaster has emerged as a promising invertebrate model to investigate innate immunity because of its well-characterized genetics. Insects are also vectors of numerous parasites which can trigger an immune response. We have investigated the interaction of Drosophila melanogaster with the flagellate protozoan Crithidia spp. We show that a per os parasitic infection triggers the synthesis of several antimicrobial peptides. By reverse phase HPLC and mass spectrometry, peptides were shown to be present in the hemolymph and not in the gut tissue, suggesting the presence of immune messengers between the site of the infection, namely the gut, and the fat body, the main site of synthesis for antimicrobial peptides. Interestingly, we have identified one molecule which is specifically induced in the hemolymph after infection with Crithidia, but not with bacteria, suggesting that Drosophila can discriminate between pathogens. When flagellates were injected into the hemolymph, a low synthesis of antimicrobial peptides was observed together with phagocytosis of parasites by circulating hemocytes. The data presented here suggest that Drosophila-Crithidia spp. represents an interesting model to study host defense against protozoan parasites.},
keywords = {Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Crithidia, Defensins, Gene Expression, Glycopeptides, Hemocytes, imler, Insect Proteins, M3i, Phagocytosis},
pubstate = {published},
tppubtype = {article}
}
Insects are able to recognize invading microorganisms and to mount an immune response to bacterial and fungal infections. Recently, the fruitfly Drosophila melanogaster has emerged as a promising invertebrate model to investigate innate immunity because of its well-characterized genetics. Insects are also vectors of numerous parasites which can trigger an immune response. We have investigated the interaction of Drosophila melanogaster with the flagellate protozoan Crithidia spp. We show that a per os parasitic infection triggers the synthesis of several antimicrobial peptides. By reverse phase HPLC and mass spectrometry, peptides were shown to be present in the hemolymph and not in the gut tissue, suggesting the presence of immune messengers between the site of the infection, namely the gut, and the fat body, the main site of synthesis for antimicrobial peptides. Interestingly, we have identified one molecule which is specifically induced in the hemolymph after infection with Crithidia, but not with bacteria, suggesting that Drosophila can discriminate between pathogens. When flagellates were injected into the hemolymph, a low synthesis of antimicrobial peptides was observed together with phagocytosis of parasites by circulating hemocytes. The data presented here suggest that Drosophila-Crithidia spp. represents an interesting model to study host defense against protozoan parasites.
Imler Jean-Luc, Hoffmann Jules A
Toll receptors in innate immunity Journal Article
In: Trends in Cell Biology, vol. 11, no. 7, pp. 304–311, 2001, ISSN: 0962-8924.
Abstract | BibTeX | Tags: Animals, Cell Surface, hoffmann, Humans, imler, Immunity, Immunologic, Innate, M3i, Membrane Glycoproteins, Membrane Proteins, Receptors, Toll-Like Receptors
@article{imler_toll_2001,
title = {Toll receptors in innate immunity},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {0962-8924},
year = {2001},
date = {2001-01-01},
journal = {Trends in Cell Biology},
volume = {11},
number = {7},
pages = {304--311},
abstract = {Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to infectious agents. In addition, the cells and molecules operating during this early stage of the immune response in vertebrates have a decisive impact on the shaping of the subsequent adaptive response. Genetic studies initially performed in the fruitfly Drosophila and later in mice have revealed the importance of proteins of the Toll family in the innate immune response. We present here our current understanding of the role of this evolutionary ancient family of proteins that are thought to function as cytokine receptors (Toll in Drosophila) or pattern-recognition receptors (TLRs in mammals) and activate similar, albeit non-identical, signal-transduction pathways in flies and mammals.},
keywords = {Animals, Cell Surface, hoffmann, Humans, imler, Immunity, Immunologic, Innate, M3i, Membrane Glycoproteins, Membrane Proteins, Receptors, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to infectious agents. In addition, the cells and molecules operating during this early stage of the immune response in vertebrates have a decisive impact on the shaping of the subsequent adaptive response. Genetic studies initially performed in the fruitfly Drosophila and later in mice have revealed the importance of proteins of the Toll family in the innate immune response. We present here our current understanding of the role of this evolutionary ancient family of proteins that are thought to function as cytokine receptors (Toll in Drosophila) or pattern-recognition receptors (TLRs in mammals) and activate similar, albeit non-identical, signal-transduction pathways in flies and mammals.
2000
Tauszig Servane, Jouanguy Emmanuelle, Hoffmann Jules A, Imler Jean-Luc
Toll-related receptors and the control of antimicrobial peptide expression in Drosophila Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 19, pp. 10520–10525, 2000, ISSN: 0027-8424.
Abstract | Links | BibTeX | Tags: Amino Acid, Animals, Anti-Bacterial Agents, Blotting, Cell Line, Cell Surface, hoffmann, imler, M3i, Membrane Glycoproteins, Multigene Family, Northern, Peptides, Receptors, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptors
@article{tauszig_toll-related_2000,
title = {Toll-related receptors and the control of antimicrobial peptide expression in Drosophila},
author = {Servane Tauszig and Emmanuelle Jouanguy and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1073/pnas.180130797},
issn = {0027-8424},
year = {2000},
date = {2000-09-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {97},
number = {19},
pages = {10520--10525},
abstract = {Insects defend themselves against infectious microorganisms by synthesizing potent antimicrobial peptides. Drosophila has appeared in recent years as a favorable model to study this innate host defense. A genetic analysis of the regulation of the antifungal peptide drosomycin has demonstrated a key role for the transmembrane receptor Toll, which prompted the search for mammalian homologs. Two of these, Toll-like receptor (TLR)2 and TLR4, recently were shown to play a critical role in innate immunity against bacteria. Here we describe six additional Toll-related genes (Toll-3 to Toll-8) in Drosophila in addition to 18-wheeler. Two of these genes, Toll-3 and Toll-4, are expressed at a low level. Toll-6, -7, and -8, on the other hand, are expressed at high levels during embryogenesis and molting, suggesting that, like Toll and 18w, they perform developmental functions. Finally, Toll-5 is expressed only in larvae and adults. By using chimeric constructs, we have tested the capacity of the signaling Toll/IL-1R homology domains of these receptors to activate antimicrobial peptide promoters and found that only Toll and Toll-5 can activate the drosomycin promoter in transfected cells, thus demonstrating specificity at the level of the Toll/IL-1R homology domain. In contrast, none of these constructs activated antibacterial peptide promoters, suggesting that Toll-related receptors are not involved in the regulation of antibacterial peptide expression. This result was independently confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide.},
keywords = {Amino Acid, Animals, Anti-Bacterial Agents, Blotting, Cell Line, Cell Surface, hoffmann, imler, M3i, Membrane Glycoproteins, Multigene Family, Northern, Peptides, Receptors, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Insects defend themselves against infectious microorganisms by synthesizing potent antimicrobial peptides. Drosophila has appeared in recent years as a favorable model to study this innate host defense. A genetic analysis of the regulation of the antifungal peptide drosomycin has demonstrated a key role for the transmembrane receptor Toll, which prompted the search for mammalian homologs. Two of these, Toll-like receptor (TLR)2 and TLR4, recently were shown to play a critical role in innate immunity against bacteria. Here we describe six additional Toll-related genes (Toll-3 to Toll-8) in Drosophila in addition to 18-wheeler. Two of these genes, Toll-3 and Toll-4, are expressed at a low level. Toll-6, -7, and -8, on the other hand, are expressed at high levels during embryogenesis and molting, suggesting that, like Toll and 18w, they perform developmental functions. Finally, Toll-5 is expressed only in larvae and adults. By using chimeric constructs, we have tested the capacity of the signaling Toll/IL-1R homology domains of these receptors to activate antimicrobial peptide promoters and found that only Toll and Toll-5 can activate the drosomycin promoter in transfected cells, thus demonstrating specificity at the level of the Toll/IL-1R homology domain. In contrast, none of these constructs activated antibacterial peptide promoters, suggesting that Toll-related receptors are not involved in the regulation of antibacterial peptide expression. This result was independently confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide.
Imler Jean-Luc, Hoffmann Jules A
Signaling mechanisms in the antimicrobial host defense of Drosophila Journal Article
In: Current Opinion in Microbiology, vol. 3, no. 1, pp. 16–22, 2000, ISSN: 1369-5274.
Abstract | BibTeX | Tags: Animals, Anti-Infective Agents, Cell Surface, Gene Expression Regulation, Genes, hoffmann, imler, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, Signal Transduction, Toll-Like Receptors
@article{imler_signaling_2000,
title = {Signaling mechanisms in the antimicrobial host defense of Drosophila},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {1369-5274},
year = {2000},
date = {2000-02-01},
journal = {Current Opinion in Microbiology},
volume = {3},
number = {1},
pages = {16--22},
abstract = {Drosophila has appeared in recent years as a powerful model to study innate immunity. Several papers published in the past year shed light on the role of the three Rel proteins Dorsal, Dif and Relish in the regulation of antimicrobial peptide expression. In addition, the discovery that a blood serine protease inhibitor is involved in the control of the antifungal response indicates that Toll is activated upon triggering of a proteolytic cascade and does not function as a Drosophila pattern recognition receptor.},
keywords = {Animals, Anti-Infective Agents, Cell Surface, Gene Expression Regulation, Genes, hoffmann, imler, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Drosophila has appeared in recent years as a powerful model to study innate immunity. Several papers published in the past year shed light on the role of the three Rel proteins Dorsal, Dif and Relish in the regulation of antimicrobial peptide expression. In addition, the discovery that a blood serine protease inhibitor is involved in the control of the antifungal response indicates that Toll is activated upon triggering of a proteolytic cascade and does not function as a Drosophila pattern recognition receptor.
Reichhart Jean-Marc, Imler Jean-Luc
Toll Story Journal Article
In: Médecine Sciences: M/S, vol. 16, pp. 1439–1442, 2000.
BibTeX | Tags: imler, M3i, reichhart
@article{reichhart_toll_2000,
title = {Toll Story},
author = {Jean-Marc Reichhart and Jean-Luc Imler},
year = {2000},
date = {2000-01-01},
journal = {Médecine Sciences: M/S},
volume = {16},
pages = {1439--1442},
keywords = {imler, M3i, reichhart},
pubstate = {published},
tppubtype = {article}
}
Tzou P, Ohresser S, Ferrandon Dominique, Capovilla Maria, Reichhart Jean-Marc, Lemaitre Bruno, Hoffmann Jules A, Imler Jean-Luc
Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia Journal Article
In: Immunity, vol. 13, pp. 737–48., 2000, ISSN: 1074-7613.
Abstract | BibTeX | Tags: *Genes, Animal, Anti-Infective Agents/*immunology/metabolism, Drosophila/genetics/*immunology, ferrandon, Gene Expression Regulation/*immunology, Genes, Glycoside Hydrolases/immunology, hoffmann, Human, imler, Insect, Insect Proteins/genetics/immunology, M3i, Non-U.S. Gov't, Organ Specificity, P.H.S., reichhart, Reporter, Support, Transfection, U.S. Gov't
@article{tzou_tissue-specific_2000b,
title = {Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia},
author = {P Tzou and S Ohresser and Dominique Ferrandon and Maria Capovilla and Jean-Marc Reichhart and Bruno Lemaitre and Jules A Hoffmann and Jean-Luc Imler},
issn = {1074-7613},
year = {2000},
date = {2000-01-01},
journal = {Immunity},
volume = {13},
pages = {737--48.},
abstract = {The production of antimicrobial peptides is an important aspect of host defense in multicellular organisms. In Drosophila, seven antimicrobial peptides with different spectra of activities are synthesized by the fat body during the immune response and secreted into the hemolymph. Using GFP reporter transgenes, we show here that all seven Drosophila antimicrobial peptides can be induced in surface epithelia in a tissue-specific manner. The imd gene plays a critical role in the activation of this local response to infection. In particular, drosomycin expression, which is regulated by the Toll pathway during the systemic response, is regulated by imd in the respiratory tract, thus demonstrating the existence of distinct regulatory mechanisms for local and systemic induction of antimicrobial peptide genes in Drosophila.},
keywords = {*Genes, Animal, Anti-Infective Agents/*immunology/metabolism, Drosophila/genetics/*immunology, ferrandon, Gene Expression Regulation/*immunology, Genes, Glycoside Hydrolases/immunology, hoffmann, Human, imler, Insect, Insect Proteins/genetics/immunology, M3i, Non-U.S. Gov't, Organ Specificity, P.H.S., reichhart, Reporter, Support, Transfection, U.S. Gov't},
pubstate = {published},
tppubtype = {article}
}
The production of antimicrobial peptides is an important aspect of host defense in multicellular organisms. In Drosophila, seven antimicrobial peptides with different spectra of activities are synthesized by the fat body during the immune response and secreted into the hemolymph. Using GFP reporter transgenes, we show here that all seven Drosophila antimicrobial peptides can be induced in surface epithelia in a tissue-specific manner. The imd gene plays a critical role in the activation of this local response to infection. In particular, drosomycin expression, which is regulated by the Toll pathway during the systemic response, is regulated by imd in the respiratory tract, thus demonstrating the existence of distinct regulatory mechanisms for local and systemic induction of antimicrobial peptide genes in Drosophila.
Imler Jean-Luc, Tauszig Servane, Jouanguy Emmanuelle, Forestier C, Hoffmann Jules A
LPS-induced immune response in Drosophila Journal Article
In: Journal of Endotoxin Research, vol. 6, no. 6, pp. 459–462, 2000, ISSN: 0968-0519.
Abstract | BibTeX | Tags: Animals, Biological, Cell Line, Cell Surface, Defensins, Genes, Genetic, hoffmann, imler, Insect, Insect Proteins, Lipopolysaccharides, M3i, Membrane Glycoproteins, Models, Mutation, Promoter Regions, Receptors, Signal Transduction, Toll-Like Receptors
@article{imler_lps-induced_2000,
title = {LPS-induced immune response in Drosophila},
author = {Jean-Luc Imler and Servane Tauszig and Emmanuelle Jouanguy and C Forestier and Jules A Hoffmann},
issn = {0968-0519},
year = {2000},
date = {2000-01-01},
journal = {Journal of Endotoxin Research},
volume = {6},
number = {6},
pages = {459--462},
abstract = {The study of the regulation of the inducible synthesis of antimicrobial peptides in Drosophila melanogaster has established this insect as a powerful model in which to study innate immunity. In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity. We report here that injection of LPS into flies induces an immune response, suggesting that LPS receptors are used in Drosophila to detect Gram-negative bacteria infection. We have identified in the recently sequenced genome of Drosophila eight genes coding for Toll-like receptors in addition to Toll, which may function as LPS receptors. However, overexpression of a selection of these genes in tissue-culture cells does not result in up-regulation of the antibacterial peptide genes. These results are discussed in light of the recent data from genetic screens aimed at identifying the genes controlling the antibacterial response in Drosophila.},
keywords = {Animals, Biological, Cell Line, Cell Surface, Defensins, Genes, Genetic, hoffmann, imler, Insect, Insect Proteins, Lipopolysaccharides, M3i, Membrane Glycoproteins, Models, Mutation, Promoter Regions, Receptors, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
The study of the regulation of the inducible synthesis of antimicrobial peptides in Drosophila melanogaster has established this insect as a powerful model in which to study innate immunity. In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity. We report here that injection of LPS into flies induces an immune response, suggesting that LPS receptors are used in Drosophila to detect Gram-negative bacteria infection. We have identified in the recently sequenced genome of Drosophila eight genes coding for Toll-like receptors in addition to Toll, which may function as LPS receptors. However, overexpression of a selection of these genes in tissue-culture cells does not result in up-regulation of the antibacterial peptide genes. These results are discussed in light of the recent data from genetic screens aimed at identifying the genes controlling the antibacterial response in Drosophila.
Imler Jean-Luc, Hoffmann Jules A
Toll and Toll-like proteins: an ancient family of receptors signaling infection Journal Article
In: Reviews in Immunogenetics, vol. 2, no. 3, pp. 294–304, 2000, ISSN: 1398-1714.
Abstract | BibTeX | Tags: Adaptor Proteins, Animals, Antigens, Autoantigens, CD14, Cell Adhesion Molecules, Cell Surface, Differentiation, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, I-kappa B Proteins, imler, Immunity, Immunologic, infection, Innate, Insect Proteins, Interleukin-1 Receptor-Associated Kinases, Knockout, Larva, Lipopolysaccharides, M3i, Mammals, MAP Kinase Signaling System, Membrane Glycoproteins, Membrane Proteins, Mice, Multigene Family, Myeloid Differentiation Factor 88, NF-kappa B, peptidoglycan, Phosphorylation, Post-Translational, Protein Kinases, Protein Processing, Protein Structure, Receptors, Recombinant Fusion Proteins, Signal Transducing, Signal Transduction, Teichoic Acids, Tertiary, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptor 6, Toll-Like Receptor 9, Toll-Like Receptors, Ubiquitins
@article{imler_toll_2000,
title = {Toll and Toll-like proteins: an ancient family of receptors signaling infection},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {1398-1714},
year = {2000},
date = {2000-01-01},
journal = {Reviews in Immunogenetics},
volume = {2},
number = {3},
pages = {294--304},
abstract = {Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to microbes. It involves intracellular signaling pathways in the fruit-fly Drosophila and in mammals that show striking similarities. Recent genetic and biochemical data have revealed, in particular, that proteins of the Toll family play a critical role in the immediate response to infection. We review here the recent developments on the structural and functional characterization of this evolutionary ancient and important family of proteins, which can function as cytokine receptors (Toll in Drosophila) or pattern recognition receptors (TLR4 in mammals) and activate similar, albeit non identical signal transduction pathways, in flies and mammals.},
keywords = {Adaptor Proteins, Animals, Antigens, Autoantigens, CD14, Cell Adhesion Molecules, Cell Surface, Differentiation, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, I-kappa B Proteins, imler, Immunity, Immunologic, infection, Innate, Insect Proteins, Interleukin-1 Receptor-Associated Kinases, Knockout, Larva, Lipopolysaccharides, M3i, Mammals, MAP Kinase Signaling System, Membrane Glycoproteins, Membrane Proteins, Mice, Multigene Family, Myeloid Differentiation Factor 88, NF-kappa B, peptidoglycan, Phosphorylation, Post-Translational, Protein Kinases, Protein Processing, Protein Structure, Receptors, Recombinant Fusion Proteins, Signal Transducing, Signal Transduction, Teichoic Acids, Tertiary, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptor 6, Toll-Like Receptor 9, Toll-Like Receptors, Ubiquitins},
pubstate = {published},
tppubtype = {article}
}
Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to microbes. It involves intracellular signaling pathways in the fruit-fly Drosophila and in mammals that show striking similarities. Recent genetic and biochemical data have revealed, in particular, that proteins of the Toll family play a critical role in the immediate response to infection. We review here the recent developments on the structural and functional characterization of this evolutionary ancient and important family of proteins, which can function as cytokine receptors (Toll in Drosophila) or pattern recognition receptors (TLR4 in mammals) and activate similar, albeit non identical signal transduction pathways, in flies and mammals.
1998
Levashina Elena A, Ohresser S, Lemaitre Bruno, Imler Jean-Luc
Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowin Journal Article
In: Journal of Molecular Biology, vol. 278, no. 3, pp. 515–527, 1998, ISSN: 0022-2836.
Abstract | Links | BibTeX | Tags: Animals, Anti-Infective Agents, Antimicrobial Cationic Peptides, Base Sequence, Cloning, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Glycopeptides, imler, Insect, Insect Proteins, Larva, M3i, Molecular, Mutation, Peptides, Promoter Regions, Recombinant Fusion Proteins, Reporter, Restriction Mapping, Transcription
@article{levashina_two_1998,
title = {Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowin},
author = {Elena A Levashina and S Ohresser and Bruno Lemaitre and Jean-Luc Imler},
doi = {10.1006/jmbi.1998.1705},
issn = {0022-2836},
year = {1998},
date = {1998-01-01},
journal = {Journal of Molecular Biology},
volume = {278},
number = {3},
pages = {515--527},
abstract = {Metchnikowin is a recently discovered proline-rich peptide from Drosophila with antibacterial and antifungal properties. Like most other antimicrobial peptides from insects, its expression is immune-inducible. Here we present evidence that induction of metchnikowin gene expression can be mediated either by the TOLL pathway or by the imd gene product. We show that the gene remains inducible in Toll-deficient mutants, in which the antifungal response is blocked, as well as in imd mutants, which fail to mount an antibacterial response. However, in Toll-deficient;imd double mutants, metchnikowin gene expression can no longer be detected after immune challenge. Our results suggest that expression of this peptide with dual activity can be triggered by signals generated by either bacterial or fungal infection. Cloning of the metchnikowin gene revealed the presence in the 5' flanking region of several putative cis-regulatory motifs characterized in the promoters of insect immune genes: namely, Rel sites, GATA motifs, interferon consensus response elements and NF-IL6 response elements. Establishment of transgenic fly lines in which the GFP reporter gene was placed under the control of 1.5 kb of metchnikowin gene upstream sequences indicates that this fragment is able to confer full immune inducibility and tissue specificity of expression on the transgene.},
keywords = {Animals, Anti-Infective Agents, Antimicrobial Cationic Peptides, Base Sequence, Cloning, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Glycopeptides, imler, Insect, Insect Proteins, Larva, M3i, Molecular, Mutation, Peptides, Promoter Regions, Recombinant Fusion Proteins, Reporter, Restriction Mapping, Transcription},
pubstate = {published},
tppubtype = {article}
}
Metchnikowin is a recently discovered proline-rich peptide from Drosophila with antibacterial and antifungal properties. Like most other antimicrobial peptides from insects, its expression is immune-inducible. Here we present evidence that induction of metchnikowin gene expression can be mediated either by the TOLL pathway or by the imd gene product. We show that the gene remains inducible in Toll-deficient mutants, in which the antifungal response is blocked, as well as in imd mutants, which fail to mount an antibacterial response. However, in Toll-deficient;imd double mutants, metchnikowin gene expression can no longer be detected after immune challenge. Our results suggest that expression of this peptide with dual activity can be triggered by signals generated by either bacterial or fungal infection. Cloning of the metchnikowin gene revealed the presence in the 5' flanking region of several putative cis-regulatory motifs characterized in the promoters of insect immune genes: namely, Rel sites, GATA motifs, interferon consensus response elements and NF-IL6 response elements. Establishment of transgenic fly lines in which the GFP reporter gene was placed under the control of 1.5 kb of metchnikowin gene upstream sequences indicates that this fragment is able to confer full immune inducibility and tissue specificity of expression on the transgene.
1997
Dimarcq Jean-Luc, Imler Jean-Luc, Lanot R, Ezekowitz Alan R B, Hoffmann Jules A, Janeway C A, Lagueux Marie
Treatment of l(2)mbn Drosophila tumorous blood cells with the steroid hormone ecdysone amplifies the inducibility of antimicrobial peptide gene expression Journal Article
In: Insect Biochemistry and Molecular Biology, vol. 27, no. 10, pp. 877–886, 1997, ISSN: 0965-1748.
Abstract | BibTeX | Tags: Animals, Bacterial Infections, Cellular, Ecdysone, Gene Expression, Genes, Hemocytes, Hemolymph, hoffmann, imler, Immunity, Insect, M3i, Macrophages, Peptide Biosynthesis, Phagocytosis
@article{dimarcq_treatment_1997,
title = {Treatment of l(2)mbn Drosophila tumorous blood cells with the steroid hormone ecdysone amplifies the inducibility of antimicrobial peptide gene expression},
author = {Jean-Luc Dimarcq and Jean-Luc Imler and R Lanot and Alan R B Ezekowitz and Jules A Hoffmann and C A Janeway and Marie Lagueux},
issn = {0965-1748},
year = {1997},
date = {1997-10-01},
journal = {Insect Biochemistry and Molecular Biology},
volume = {27},
number = {10},
pages = {877--886},
abstract = {Insects rely on both humoral and cellular mechanisms to defend themselves against microbial infections. The humoral response involves synthesis of a battery of potent antimicrobial peptides by the fat body and, to a lesser extent, by blood cells. The cellular response on the other hand consists of phagocytosis of small microorganisms and melanization and encapsulation of larger parasites. The l(2)mbn cell line, established from tumorous larval hemocytes, represents a system of choice to dissect the molecular events controlling cellular immunity. We report here that l(2)mbn cells can be efficiently induced to differentiate in adherent, macrophage-like cells by treatment with 20-hydroxyecdysone. Ecdysone treatment increases both the phagocytic capacity of l(2)mbn cells and their competence to express antimicrobial genes in response to immune challenge. We also report that expression of several regulatory molecules thought to be involved in the immune response is up-regulated by ecdysone in l(2)mbn cells.},
keywords = {Animals, Bacterial Infections, Cellular, Ecdysone, Gene Expression, Genes, Hemocytes, Hemolymph, hoffmann, imler, Immunity, Insect, M3i, Macrophages, Peptide Biosynthesis, Phagocytosis},
pubstate = {published},
tppubtype = {article}
}
Insects rely on both humoral and cellular mechanisms to defend themselves against microbial infections. The humoral response involves synthesis of a battery of potent antimicrobial peptides by the fat body and, to a lesser extent, by blood cells. The cellular response on the other hand consists of phagocytosis of small microorganisms and melanization and encapsulation of larger parasites. The l(2)mbn cell line, established from tumorous larval hemocytes, represents a system of choice to dissect the molecular events controlling cellular immunity. We report here that l(2)mbn cells can be efficiently induced to differentiate in adherent, macrophage-like cells by treatment with 20-hydroxyecdysone. Ecdysone treatment increases both the phagocytic capacity of l(2)mbn cells and their competence to express antimicrobial genes in response to immune challenge. We also report that expression of several regulatory molecules thought to be involved in the immune response is up-regulated by ecdysone in l(2)mbn cells.
