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2002
Hoffmann Jules A, Reichhart Jean-Marc
Drosophila innate immunity: an evolutionary perspective Article de journal
Dans: Nat. Immunol., vol. 3, no. 2, p. 121–126, 2002, ISSN: 1529-2908.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biological Evolution, Cell Surface, hoffmann, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptors
@article{hoffmann_drosophila_2002,
title = {Drosophila innate immunity: an evolutionary perspective},
author = {Jules A Hoffmann and Jean-Marc Reichhart},
doi = {10.1038/ni0202-121},
issn = {1529-2908},
year = {2002},
date = {2002-02-01},
journal = {Nat. Immunol.},
volume = {3},
number = {2},
pages = {121--126},
abstract = {In response to microbial infections, Drosophila mounts a multifaceted immune response involving humoral reactions that culminate in the destruction of invading organisms by lytic peptides. These defense mechanisms are activated via two distinct signaling pathways. One of these, the Toll pathway, controls resistance to fungal and Gram-positive bacterial infections, whereas the Imd pathway is responsible for defense against Gram-negative bacterial infections. Current evidence indicates that recognition of infectious nonself agents results from interactions between microbial wall components and extracellular pattern recognition proteins. We discuss here evolutionary perspectives on our present understanding of the antimicrobial defenses of Drosophila.},
keywords = {Animals, Biological Evolution, Cell Surface, hoffmann, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
In response to microbial infections, Drosophila mounts a multifaceted immune response involving humoral reactions that culminate in the destruction of invading organisms by lytic peptides. These defense mechanisms are activated via two distinct signaling pathways. One of these, the Toll pathway, controls resistance to fungal and Gram-positive bacterial infections, whereas the Imd pathway is responsible for defense against Gram-negative bacterial infections. Current evidence indicates that recognition of infectious nonself agents results from interactions between microbial wall components and extracellular pattern recognition proteins. We discuss here evolutionary perspectives on our present understanding of the antimicrobial defenses of Drosophila.
Ligoxygakis Petros, Bulet Philippe, Reichhart Jean-Marc
Critical evaluation of the role of the Toll-like receptor 18-Wheeler in the host defense of Drosophila Article de journal
Dans: EMBO Rep., vol. 3, no. 7, p. 666–673, 2002, ISSN: 1469-221X.
Résumé | Liens | BibTeX | Étiquettes: Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Cell Adhesion Molecules, Fat Body, Gene Expression Regulation, Genes, Immunohistochemistry, Immunologic, Insect, Insect Proteins, Larva, M3i, Mass, Matrix-Assisted Laser Desorption-Ionization, Membrane Proteins, Receptors, reichhart, Reporter, Spectrometry, Transgenes
@article{ligoxygakis_critical_2002,
title = {Critical evaluation of the role of the Toll-like receptor 18-Wheeler in the host defense of Drosophila},
author = {Petros Ligoxygakis and Philippe Bulet and Jean-Marc Reichhart},
doi = {10.1093/embo-reports/kvf130},
issn = {1469-221X},
year = {2002},
date = {2002-01-01},
journal = {EMBO Rep.},
volume = {3},
number = {7},
pages = {666--673},
abstract = {Essential aspects of innate immune responses to microbial infections appear to be conserved between insects and mammals. In particular, in both groups, transmembrane receptors of the Toll superfamily play a crucial role in activating immune defenses. The Drosophila Toll family member 18-Wheeler had been proposed to sense Gram-negative infection and direct selective expression of peptides active against Gram-negative bacteria. Here we re-examine the role of 18-Wheeler and show that in adults it is dispensable for immune responses. In larvae, 18wheeler is required for normal fat body development, and in mutant larvae induction of all antimicrobial peptide genes, and not only of those directed against Gram-negative bacteria, is compromised. 18-Wheeler does not qualify as a pattern recognition receptor of Gram-negative bacteria.},
keywords = {Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Cell Adhesion Molecules, Fat Body, Gene Expression Regulation, Genes, Immunohistochemistry, Immunologic, Insect, Insect Proteins, Larva, M3i, Mass, Matrix-Assisted Laser Desorption-Ionization, Membrane Proteins, Receptors, reichhart, Reporter, Spectrometry, Transgenes},
pubstate = {published},
tppubtype = {article}
}
Essential aspects of innate immune responses to microbial infections appear to be conserved between insects and mammals. In particular, in both groups, transmembrane receptors of the Toll superfamily play a crucial role in activating immune defenses. The Drosophila Toll family member 18-Wheeler had been proposed to sense Gram-negative infection and direct selective expression of peptides active against Gram-negative bacteria. Here we re-examine the role of 18-Wheeler and show that in adults it is dispensable for immune responses. In larvae, 18wheeler is required for normal fat body development, and in mutant larvae induction of all antimicrobial peptide genes, and not only of those directed against Gram-negative bacteria, is compromised. 18-Wheeler does not qualify as a pattern recognition receptor of Gram-negative bacteria.
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 Article de journal
Dans: Genesis (New York, N.Y.: 2000), vol. 34, no. 1-2, p. 160–164, 2002, ISSN: 1526-954X.
Liens | BibTeX | Étiquettes: 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}
}
Tzou P, Reichhart Jean-Marc, Lemaitre Bruno
Over-expression of a single antimicrobial peptide restores wild-type resistance to infection in immuno-deficient Drosophila mutants. Article de journal
Dans: Proc. Natl. Acad. Sci. U S A, vol. 99, p. 2152–2157, 2002.
Résumé | BibTeX | Étiquettes: M3i, reichhart
@article{tzou_over-expression_2002,
title = {Over-expression of a single antimicrobial peptide restores wild-type resistance to infection in immuno-deficient Drosophila mutants.},
author = {P Tzou and Jean-Marc Reichhart and Bruno Lemaitre},
year = {2002},
date = {2002-01-01},
journal = {Proc. Natl. Acad. Sci. U S A},
volume = {99},
pages = {2152--2157},
abstract = {The analysis of the in vivo relevance of the antimicrobial peptides (AMPs) for Drosophila resistance against microbial infection is complicated by the numerous AMP genes present in this organism, as well as the redundant defence mechanism within the innate immune system. Mutants deficient for both the Imd and Toll pathway failed to express any AMP genes after infection and are extremely susceptible to both fungal and bacterial infections. To study unambiguously the in vivo role of each antimicrobial peptide in the Drosophila host defence, we have generated imd; spz double mutant flies that over-express a peptide driven by a transgene under a constitutive promoter. Our results clearly show that over-expression of certain peptides are sufficient to rescue the imd; spz susceptibility to microbial infection, supporting the important role of AMPs in Drosophila host defence.},
keywords = {M3i, reichhart},
pubstate = {published},
tppubtype = {article}
}
The analysis of the in vivo relevance of the antimicrobial peptides (AMPs) for Drosophila resistance against microbial infection is complicated by the numerous AMP genes present in this organism, as well as the redundant defence mechanism within the innate immune system. Mutants deficient for both the Imd and Toll pathway failed to express any AMP genes after infection and are extremely susceptible to both fungal and bacterial infections. To study unambiguously the in vivo role of each antimicrobial peptide in the Drosophila host defence, we have generated imd; spz double mutant flies that over-express a peptide driven by a transgene under a constitutive promoter. Our results clearly show that over-expression of certain peptides are sufficient to rescue the imd; spz susceptibility to microbial infection, supporting the important role of AMPs in Drosophila host defence.
2001
Irving Phil, Troxler Laurent, Heuer Timothy S, Belvin Marcia, Kopczynski Casey, Reichhart Jean-Marc, Hoffmann Jules A, Hetru Charles
A genome-wide analysis of immune responses in Drosophila Article de journal
Dans: Proc. Natl. Acad. Sci. U.S.A., vol. 98, no. 26, p. 15119–15124, 2001, ISSN: 0027-8424.
Résumé | Liens | BibTeX | Étiquettes: Animals, bioinformatic, Gene Expression Regulation, Genome, Gram-Negative Bacteria, hoffmann, M3i, Male, Oligonucleotide Array Sequence Analysis, reichhart, Signal Transduction
@article{irving_genome-wide_2001,
title = {A genome-wide analysis of immune responses in Drosophila},
author = {Phil Irving and Laurent Troxler and Timothy S Heuer and Marcia Belvin and Casey Kopczynski and Jean-Marc Reichhart and Jules A Hoffmann and Charles Hetru},
doi = {10.1073/pnas.261573998},
issn = {0027-8424},
year = {2001},
date = {2001-12-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {98},
number = {26},
pages = {15119--15124},
abstract = {Oligonucleotide DNA microarrays were used for a genome-wide analysis of immune-challenged Drosophila infected with Gram-positive or Gram-negative bacteria, or with fungi. Aside from the expression of an established set of immune defense genes, a significant number of previously unseen immune-induced genes were found. Genes of particular interest include corin- and Stubble-like genes, both of which have a type II transmembrane domain; easter- and snake-like genes, which may fulfil the roles of easter and snake in the Toll pathway; and a masquerade-like gene, potentially involved in enzyme regulation. The microarray data has also helped to greatly reduce the number of target genes in large gene groups, such as the proteases, helping to direct the choices for future mutant studies. Many of the up-regulated genes fit into the current conceptual framework of host defense, whereas others, including the substantial number of genes with unknown functions, offer new avenues for research.},
keywords = {Animals, bioinformatic, Gene Expression Regulation, Genome, Gram-Negative Bacteria, hoffmann, M3i, Male, Oligonucleotide Array Sequence Analysis, reichhart, Signal Transduction},
pubstate = {published},
tppubtype = {article}
}
Oligonucleotide DNA microarrays were used for a genome-wide analysis of immune-challenged Drosophila infected with Gram-positive or Gram-negative bacteria, or with fungi. Aside from the expression of an established set of immune defense genes, a significant number of previously unseen immune-induced genes were found. Genes of particular interest include corin- and Stubble-like genes, both of which have a type II transmembrane domain; easter- and snake-like genes, which may fulfil the roles of easter and snake in the Toll pathway; and a masquerade-like gene, potentially involved in enzyme regulation. The microarray data has also helped to greatly reduce the number of target genes in large gene groups, such as the proteases, helping to direct the choices for future mutant studies. Many of the up-regulated genes fit into the current conceptual framework of host defense, whereas others, including the substantial number of genes with unknown functions, offer new avenues for research.
Michel T, Reichhart Jean-Marc, Hoffmann Jules A, Royet Julien
Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein Article de journal
Dans: Nature, vol. 414, no. 6865, p. 756–759, 2001, ISSN: 0028-0836.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Animals, Anti-Bacterial Agents, Anti-Infective Agents, Bacillus thuringiensis, Carrier Proteins, Cell Surface, Chromosome Mapping, Enterococcus faecalis, Fungi, Genes, Gram-Positive Bacteria, Hemolymph, hoffmann, Humans, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutation, Receptors, reichhart, Sequence Homology, Toll-Like Receptors
@article{michel_drosophila_2001,
title = {Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein},
author = {T Michel and Jean-Marc Reichhart and Jules A Hoffmann and Julien Royet},
doi = {10.1038/414756a},
issn = {0028-0836},
year = {2001},
date = {2001-12-01},
journal = {Nature},
volume = {414},
number = {6865},
pages = {756--759},
abstract = {Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections. Genetic screens have identified a range of genes involved in these intracellular signalling cascades, but how they are activated by microbial infection is largely unknown. Activation of the transmembrane receptor Toll requires a proteolytically cleaved form of an extracellular cytokine-like polypeptide, Spätzle, suggesting that Toll does not itself function as a bona fide recognition receptor of microbial patterns. This is in apparent contrast with the mammalian Toll-like receptors and raises the question of which host molecules actually recognize microbial patterns to activate Toll through Spätzle. Here we present a mutation that blocks Toll activation by Gram-positive bacteria and significantly decreases resistance to this type of infection. The mutation semmelweis (seml) inactivates the gene encoding a peptidoglycan recognition protein (PGRP-SA). Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway.},
keywords = {Amino Acid, Animals, Anti-Bacterial Agents, Anti-Infective Agents, Bacillus thuringiensis, Carrier Proteins, Cell Surface, Chromosome Mapping, Enterococcus faecalis, Fungi, Genes, Gram-Positive Bacteria, Hemolymph, hoffmann, Humans, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutation, Receptors, reichhart, Sequence Homology, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections. Genetic screens have identified a range of genes involved in these intracellular signalling cascades, but how they are activated by microbial infection is largely unknown. Activation of the transmembrane receptor Toll requires a proteolytically cleaved form of an extracellular cytokine-like polypeptide, Spätzle, suggesting that Toll does not itself function as a bona fide recognition receptor of microbial patterns. This is in apparent contrast with the mammalian Toll-like receptors and raises the question of which host molecules actually recognize microbial patterns to activate Toll through Spätzle. Here we present a mutation that blocks Toll activation by Gram-positive bacteria and significantly decreases resistance to this type of infection. The mutation semmelweis (seml) inactivates the gene encoding a peptidoglycan recognition protein (PGRP-SA). Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway.
Georgel Philippe, Naitza S, Kappler Christine, Ferrandon Dominique, Zachary Daniel, Swimmer C, Kopczynski C, Duyk G, Reichhart Jean-Marc, Hoffmann Jules A
Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis Article de journal
Dans: Dev. Cell, vol. 1, no. 4, p. 503–514, 2001, ISSN: 1534-5807.
Résumé | BibTeX | Étiquettes: Animals, Anti-Infective Agents, Apoptosis, Bacterial Infections, Caspases, Chromosome Mapping, Cysteine Proteinase Inhibitors, DNA Damage, Female, ferrandon, Gene Expression, hoffmann, I-kappa B Kinase, Immunocompromised Host, In Situ Nick-End Labeling, Insect Proteins, M3i, Male, Mutation, Phenotype, Protein Structure, Protein-Serine-Threonine Kinases, reichhart, Tertiary
@article{georgel_drosophila_2001,
title = {Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis},
author = {Philippe Georgel and S Naitza and Christine Kappler and Dominique Ferrandon and Daniel Zachary and C Swimmer and C Kopczynski and G Duyk and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {1534-5807},
year = {2001},
date = {2001-10-01},
journal = {Dev. Cell},
volume = {1},
number = {4},
pages = {503--514},
abstract = {We report the molecular characterization of the immune deficiency (imd) gene, which controls antibacterial defense in Drosophila. imd encodes a protein with a death domain similar to that of mammalian RIP (receptor interacting protein), a protein that plays a role in both NF-kappaB activation and apoptosis. We show that imd functions upstream of the DmIKK signalosome and the caspase DREDD in the control of antibacterial peptide genes. Strikingly, overexpression of imd leads to constitutive transcription of these genes and to apoptosis, and both effects are blocked by coexpression of the caspase inhibitor P35. We also show that imd is involved in the apoptotic response to UV irradiation. These data raise the possibility that antibacterial response and apoptosis share common control elements in Drosophila.},
keywords = {Animals, Anti-Infective Agents, Apoptosis, Bacterial Infections, Caspases, Chromosome Mapping, Cysteine Proteinase Inhibitors, DNA Damage, Female, ferrandon, Gene Expression, hoffmann, I-kappa B Kinase, Immunocompromised Host, In Situ Nick-End Labeling, Insect Proteins, M3i, Male, Mutation, Phenotype, Protein Structure, Protein-Serine-Threonine Kinases, reichhart, Tertiary},
pubstate = {published},
tppubtype = {article}
}
We report the molecular characterization of the immune deficiency (imd) gene, which controls antibacterial defense in Drosophila. imd encodes a protein with a death domain similar to that of mammalian RIP (receptor interacting protein), a protein that plays a role in both NF-kappaB activation and apoptosis. We show that imd functions upstream of the DmIKK signalosome and the caspase DREDD in the control of antibacterial peptide genes. Strikingly, overexpression of imd leads to constitutive transcription of these genes and to apoptosis, and both effects are blocked by coexpression of the caspase inhibitor P35. We also show that imd is involved in the apoptotic response to UV irradiation. These data raise the possibility that antibacterial response and apoptosis share common control elements in Drosophila.
2000
Rutschmann Sophie, Jung Alain C, Hetru Charles, Reichhart Jean-Marc, Hoffmann Jules A, Ferrandon Dominique
The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila Article de journal
Dans: Immunity, vol. 12, no. 5, p. 569–580, 2000, ISSN: 1074-7613.
Résumé | BibTeX | Étiquettes: Animals, Antigens, Bacterial, DNA-Binding Proteins, ferrandon, Fungal, hoffmann, Immunity, Innate, M3i, reichhart, Transcription Factors
@article{rutschmann_rel_2000,
title = {The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila},
author = {Sophie Rutschmann and Alain C Jung and Charles Hetru and Jean-Marc Reichhart and Jules A Hoffmann and Dominique Ferrandon},
issn = {1074-7613},
year = {2000},
date = {2000-05-01},
journal = {Immunity},
volume = {12},
number = {5},
pages = {569--580},
abstract = {We have isolated two Drosophila lines that carry point mutations in the gene coding for the NF-KB-like factor DIF. Like mutants of the Toll pathway, Dif mutant flies are susceptible to fungal but not to bacterial infections. Genetic epistasis experiments demonstrate that Dif mediates the Toll-dependent control of the inducibility of the antifungal peptide gene Drosomycin. Strikingly, DIF alone is required for the antifungal response in adults, but is redundant in larvae with Dorsal, another Rel family member. In Drosophila, Dif appears to be dedicated to the antifungal defense elicited by fungi and gram-positive bacteria. We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals.},
keywords = {Animals, Antigens, Bacterial, DNA-Binding Proteins, ferrandon, Fungal, hoffmann, Immunity, Innate, M3i, reichhart, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
We have isolated two Drosophila lines that carry point mutations in the gene coding for the NF-KB-like factor DIF. Like mutants of the Toll pathway, Dif mutant flies are susceptible to fungal but not to bacterial infections. Genetic epistasis experiments demonstrate that Dif mediates the Toll-dependent control of the inducibility of the antifungal peptide gene Drosomycin. Strikingly, DIF alone is required for the antifungal response in adults, but is redundant in larvae with Dorsal, another Rel family member. In Drosophila, Dif appears to be dedicated to the antifungal defense elicited by fungi and gram-positive bacteria. We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals.
Green Clare, Levashina Elena A, McKimmie C, Dafforn Timothy R, Reichhart Jean-Marc, Gubb David
The necrotic gene in Drosophila corresponds to one of a cluster of three Serpin transcripts mapping at 43A1.2. Article de journal
Dans: Genetics, vol. 156, p. 1117–1127, 2000.
Résumé | BibTeX | Étiquettes: M3i, reichhart
@article{green_necrotic_2000,
title = {The necrotic gene in Drosophila corresponds to one of a cluster of three Serpin transcripts mapping at 43A1.2.},
author = {Clare Green and Elena A Levashina and C McKimmie and Timothy R Dafforn and Jean-Marc Reichhart and David Gubb},
year = {2000},
date = {2000-01-01},
journal = {Genetics},
volume = {156},
pages = {1117--1127},
abstract = {Mutants of the necrotic (nec) gene in Drosophila melanogaster die in the late pupal stage as pharate adults, or hatch as weak, but relatively normal-looking, flies. Adults develop black melanized spots on the body and leg joints, the abdomen swells with hemolymph and flies die within three or four days of eclosion. Pleiotropic nec phenotypes include melanization and cellular necrosis. These changes are consistent with activation of one, or more, proteolytic cascades. The nec gene corresponds to Spn43Ac, one of a cluster of three putative serine proteinase inhibitors at 43A1.2, on the right arm of chromosome two. Although serpins have been implicated in the activation of many diverse pathways, lack of an individual serpin rarely causes a detectable phenotype. Absence of Spn43Ac , however, gives a clear phenotype, which will allow a mutational analysis of critical features of the molecular structure of serpins.},
keywords = {M3i, reichhart},
pubstate = {published},
tppubtype = {article}
}
Mutants of the necrotic (nec) gene in Drosophila melanogaster die in the late pupal stage as pharate adults, or hatch as weak, but relatively normal-looking, flies. Adults develop black melanized spots on the body and leg joints, the abdomen swells with hemolymph and flies die within three or four days of eclosion. Pleiotropic nec phenotypes include melanization and cellular necrosis. These changes are consistent with activation of one, or more, proteolytic cascades. The nec gene corresponds to Spn43Ac, one of a cluster of three putative serine proteinase inhibitors at 43A1.2, on the right arm of chromosome two. Although serpins have been implicated in the activation of many diverse pathways, lack of an individual serpin rarely causes a detectable phenotype. Absence of Spn43Ac , however, gives a clear phenotype, which will allow a mutational analysis of critical features of the molecular structure of serpins.
Reichhart Jean-Marc, Imler Jean-Luc
Toll Story Article de journal
Dans: Médecine Sciences: M/S, vol. 16, p. 1439–1442, 2000.
BibTeX | Étiquettes: 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}
}
Ferrandon Dominique, Hetru Charles, Reichhart Jean-Marc, Hoffmann Jules A
L'immunité innée : de la drosophile à l'homme Article de journal
Dans: Pour la Science, vol. Dossier Hors Série Octobre, p. 8–12, 2000.
BibTeX | Étiquettes: ferrandon, hoffmann, M3i, reichhart
@article{ferrandon_immunite_2000,
title = {L'immunité innée : de la drosophile à l'homme},
author = {Dominique Ferrandon and Charles Hetru and Jean-Marc Reichhart and Jules A Hoffmann},
year = {2000},
date = {2000-01-01},
journal = {Pour la Science},
volume = {Dossier Hors Série Octobre},
pages = {8--12},
keywords = {ferrandon, hoffmann, 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 Article de journal
Dans: Immunity, vol. 13, p. 737–48., 2000, ISSN: 1074-7613.
Résumé | BibTeX | Étiquettes: *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.
1999
Levashina Elena A, Langley E, Green C, Gubb David, Ashburner M, Hoffmann Jules A, Reichhart Jean-Marc
Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila Article de journal
Dans: Science, vol. 285, no. 5435, p. 1917–1919, 1999, ISSN: 0036-8075.
Résumé | BibTeX | Étiquettes: Animals, Antifungal Agents, Antimicrobial Cationic Peptides, Body Patterning, Cell Surface, Escherichia coli, Genes, Hemolymph, hoffmann, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutagenesis, Peptides, Receptors, Recombinant Fusion Proteins, reichhart, Serine Proteinase Inhibitors, Serpins, Signal Transduction, Toll-Like Receptors, Up-Regulation
@article{levashina_constitutive_1999,
title = {Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila},
author = {Elena A Levashina and E Langley and C Green and David Gubb and M Ashburner and Jules A Hoffmann and Jean-Marc Reichhart},
issn = {0036-8075},
year = {1999},
date = {1999-09-01},
journal = {Science},
volume = {285},
number = {5435},
pages = {1917--1919},
abstract = {The antifungal defense of Drosophila is controlled by the spaetzle/Toll/cactus gene cassette. Here, a loss-of-function mutation in the gene encoding a blood serine protease inhibitor, Spn43Ac, was shown to lead to constitutive expression of the antifungal peptide drosomycin, and this effect was mediated by the spaetzle and Toll gene products. Spaetzle was cleaved by proteolytic enzymes to its active ligand form shortly after immune challenge, and cleaved Spaetzle was constitutively present in Spn43Ac-deficient flies. Hence, Spn43Ac negatively regulates the Toll signaling pathway, and Toll does not function as a pattern recognition receptor in the Drosophila host defense.},
keywords = {Animals, Antifungal Agents, Antimicrobial Cationic Peptides, Body Patterning, Cell Surface, Escherichia coli, Genes, Hemolymph, hoffmann, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutagenesis, Peptides, Receptors, Recombinant Fusion Proteins, reichhart, Serine Proteinase Inhibitors, Serpins, Signal Transduction, Toll-Like Receptors, Up-Regulation},
pubstate = {published},
tppubtype = {article}
}
The antifungal defense of Drosophila is controlled by the spaetzle/Toll/cactus gene cassette. Here, a loss-of-function mutation in the gene encoding a blood serine protease inhibitor, Spn43Ac, was shown to lead to constitutive expression of the antifungal peptide drosomycin, and this effect was mediated by the spaetzle and Toll gene products. Spaetzle was cleaved by proteolytic enzymes to its active ligand form shortly after immune challenge, and cleaved Spaetzle was constitutively present in Spn43Ac-deficient flies. Hence, Spn43Ac negatively regulates the Toll signaling pathway, and Toll does not function as a pattern recognition receptor in the Drosophila host defense.
Manfruelli P, Reichhart Jean-Marc, Steward R, Hoffmann Jules A, Lemaitre Bruno
A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF Article de journal
Dans: EMBO J., vol. 18, no. 12, p. 3380–3391, 1999, ISSN: 0261-4189.
Résumé | Liens | BibTeX | Étiquettes: Animals, Anti-Infective Agents, Cell Surface, Clone Cells, DNA-Binding Proteins, Fat Body, Female, Gene Expression Regulation, Genes, hoffmann, Insect, Insect Proteins, Larva, M3i, Male, Membrane Glycoproteins, Mosaicism, Mutation, Nuclear Proteins, Phosphoproteins, Receptors, reichhart, Reporter, Signal Transduction, Toll-Like Receptors, Transcription Factors
@article{manfruelli_mosaic_1999,
title = {A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF},
author = {P Manfruelli and Jean-Marc Reichhart and R Steward and Jules A Hoffmann and Bruno Lemaitre},
doi = {10.1093/emboj/18.12.3380},
issn = {0261-4189},
year = {1999},
date = {1999-06-01},
journal = {EMBO J.},
volume = {18},
number = {12},
pages = {3380--3391},
abstract = {Expression of the gene encoding the antifungal peptide Drosomycin in Drosophila adults is controlled by the Toll signaling pathway. The Rel proteins Dorsal and DIF (Dorsal-related immunity factor) are possible candidates for the transactivating protein in the Toll pathway that directly regulates the drosomycin gene. We have examined the requirement of Dorsal and DIF for drosomycin expression in larval fat body cells, the predominant immune-responsive tissue, using the yeast site-specific flp/FRT recombination system to generate cell clones homozygous for a deficiency uncovering both the dorsal and the dif genes. Here we show that in the absence of both genes, the immune-inducibility of drosomycin is lost but can be rescued by overexpression of either dorsal or dif under the control of a heat-shock promoter. This result suggests a functional redundancy between both Rel proteins in the control of drosomycin gene expression in the larvae of Drosophila. Interestingly, the gene encoding the antibacterial peptide Diptericin remains fully inducible in the absence of the dorsal and dif genes. Finally, we have used fat body cell clones homozygous for various mutations to show that a linear activation cascade Spaetzle--textgreater Toll--textgreaterCactus--textgreaterDorsal/DIF leads to the induction of the drosomycin gene in larval fat body cells.},
keywords = {Animals, Anti-Infective Agents, Cell Surface, Clone Cells, DNA-Binding Proteins, Fat Body, Female, Gene Expression Regulation, Genes, hoffmann, Insect, Insect Proteins, Larva, M3i, Male, Membrane Glycoproteins, Mosaicism, Mutation, Nuclear Proteins, Phosphoproteins, Receptors, reichhart, Reporter, Signal Transduction, Toll-Like Receptors, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
Expression of the gene encoding the antifungal peptide Drosomycin in Drosophila adults is controlled by the Toll signaling pathway. The Rel proteins Dorsal and DIF (Dorsal-related immunity factor) are possible candidates for the transactivating protein in the Toll pathway that directly regulates the drosomycin gene. We have examined the requirement of Dorsal and DIF for drosomycin expression in larval fat body cells, the predominant immune-responsive tissue, using the yeast site-specific flp/FRT recombination system to generate cell clones homozygous for a deficiency uncovering both the dorsal and the dif genes. Here we show that in the absence of both genes, the immune-inducibility of drosomycin is lost but can be rescued by overexpression of either dorsal or dif under the control of a heat-shock promoter. This result suggests a functional redundancy between both Rel proteins in the control of drosomycin gene expression in the larvae of Drosophila. Interestingly, the gene encoding the antibacterial peptide Diptericin remains fully inducible in the absence of the dorsal and dif genes. Finally, we have used fat body cell clones homozygous for various mutations to show that a linear activation cascade Spaetzle--textgreater Toll--textgreaterCactus--textgreaterDorsal/DIF leads to the induction of the drosomycin gene in larval fat body cells.
Gross I, Georgel Philippe, Oertel-Buchheit P, Schnarr M, Reichhart Jean-Marc
Dorsal-B, a splice variant of the Drosophila factor Dorsal, is a novel Rel/NF-kB transcriptional activator. Article de journal
Dans: Gene, vol. 228, p. 233–242, 1999.
Résumé | BibTeX | Étiquettes: M3i, reichhart
@article{gross_dorsal-b_1999,
title = {Dorsal-B, a splice variant of the Drosophila factor Dorsal, is a novel Rel/NF-kB transcriptional activator.},
author = {I Gross and Philippe Georgel and P Oertel-Buchheit and M Schnarr and Jean-Marc Reichhart},
year = {1999},
date = {1999-01-01},
journal = {Gene},
volume = {228},
pages = {233--242},
abstract = {The Drosophila transcription factor Dorsal, a member of the Rel/NF-kB family of proteins, plays a key role in the establishment of dorsoventral polarity in the early embryo and is also involved in the immune response. Here we present evidence that the primary transcript of dorsal can be alternatively spliced, generating Dorsal B, a new Rel/NF-kB family member. Dorsal and Dorsal B are identical in the N-terminal region which comprises both a DNA binding domain and a dimerization domain. However, Dorsal B lacks the nuclear localization signal located at the end of the Rel domain of Dorsal and is totally divergent in the C-terminal portion. Although Dorsal B by itself is not able to induce the expression of a kB-controlled Luciferase reporter gene, we demonstrate that its C-terminal portion has transactivating properties. Analysis of thedorsal B expression pattern indicates that the splicing is tissue-specific and excludes a putative role in early embryogenesis. On the other hand, Dorsal B synthesis is enhanced upon septic injury and this challenge induces a nuclear accumulation of the protein in fat body cells suggesting that it may be involved in the immune response.},
keywords = {M3i, reichhart},
pubstate = {published},
tppubtype = {article}
}
The Drosophila transcription factor Dorsal, a member of the Rel/NF-kB family of proteins, plays a key role in the establishment of dorsoventral polarity in the early embryo and is also involved in the immune response. Here we present evidence that the primary transcript of dorsal can be alternatively spliced, generating Dorsal B, a new Rel/NF-kB family member. Dorsal and Dorsal B are identical in the N-terminal region which comprises both a DNA binding domain and a dimerization domain. However, Dorsal B lacks the nuclear localization signal located at the end of the Rel domain of Dorsal and is totally divergent in the C-terminal portion. Although Dorsal B by itself is not able to induce the expression of a kB-controlled Luciferase reporter gene, we demonstrate that its C-terminal portion has transactivating properties. Analysis of thedorsal B expression pattern indicates that the splicing is tissue-specific and excludes a putative role in early embryogenesis. On the other hand, Dorsal B synthesis is enhanced upon septic injury and this challenge induces a nuclear accumulation of the protein in fat body cells suggesting that it may be involved in the immune response.
1998
Ferrandon Dominique, Jung Alain C, Criqui M, Lemaitre Bruno, Uttenweiler-Joseph S, Michaut Lydia, Reichhart Jean-Marc, Hoffmann Jules A
A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway Article de journal
Dans: EMBO J., vol. 17, no. 5, p. 1217–1227, 1998, ISSN: 0261-4189.
Résumé | Liens | BibTeX | Étiquettes: Animals, bacteria, Cell Surface, Developmental, Digestive System, Epithelium, Fat Body, Female, ferrandon, Fungal, Gene Expression Regulation, Genes, Green Fluorescent Proteins, hoffmann, Insect Proteins, Larva, Luminescent Proteins, M3i, Male, Membrane Glycoproteins, Organ Specificity, Receptors, reichhart, Reporter, Respiratory System, Spores, Toll-Like Receptors, Trachea, Transgenes
@article{ferrandon_drosomycin-gfp_1998,
title = {A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway},
author = {Dominique Ferrandon and Alain C Jung and M Criqui and Bruno Lemaitre and S Uttenweiler-Joseph and Lydia Michaut and Jean-Marc Reichhart and Jules A Hoffmann},
doi = {10.1093/emboj/17.5.1217},
issn = {0261-4189},
year = {1998},
date = {1998-08-01},
journal = {EMBO J.},
volume = {17},
number = {5},
pages = {1217--1227},
abstract = {A hallmark of the systemic antimicrobial response of Drosophila is the synthesis by the fat body of several antimicrobial peptides which are released into the hemolymph in response to a septic injury. One of these peptides, drosomycin, is active primarily against fungi. Using a drosomycin-green fluorescent protein (GFP) reporter gene, we now show that in addition to the fat body, a variety of epithelial tissues that are in direct contact with the external environment, including those of the respiratory, digestive and reproductive tracts, can express the antifungal peptide, suggesting a local response to infections affecting these barrier tissues. As is the case for vertebrate epithelia, insect epithelia appear to be more than passive physical barriers and are likely to constitute an active component of innate immunity. We also show that, in contrast to the systemic antifungal response, this local immune response is independent of the Toll pathway.},
keywords = {Animals, bacteria, Cell Surface, Developmental, Digestive System, Epithelium, Fat Body, Female, ferrandon, Fungal, Gene Expression Regulation, Genes, Green Fluorescent Proteins, hoffmann, Insect Proteins, Larva, Luminescent Proteins, M3i, Male, Membrane Glycoproteins, Organ Specificity, Receptors, reichhart, Reporter, Respiratory System, Spores, Toll-Like Receptors, Trachea, Transgenes},
pubstate = {published},
tppubtype = {article}
}
A hallmark of the systemic antimicrobial response of Drosophila is the synthesis by the fat body of several antimicrobial peptides which are released into the hemolymph in response to a septic injury. One of these peptides, drosomycin, is active primarily against fungi. Using a drosomycin-green fluorescent protein (GFP) reporter gene, we now show that in addition to the fat body, a variety of epithelial tissues that are in direct contact with the external environment, including those of the respiratory, digestive and reproductive tracts, can express the antifungal peptide, suggesting a local response to infections affecting these barrier tissues. As is the case for vertebrate epithelia, insect epithelia appear to be more than passive physical barriers and are likely to constitute an active component of innate immunity. We also show that, in contrast to the systemic antifungal response, this local immune response is independent of the Toll pathway.
Nicolas E, Reichhart Jean-Marc, Hoffmann Jules A, Lemaitre Bruno
In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila Article de journal
Dans: J. Biol. Chem., vol. 273, no. 17, p. 10463–10469, 1998, ISSN: 0021-9258.
Résumé | BibTeX | Étiquettes: Animals, Cell Surface, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, Insect Proteins, Larva, M3i, Membrane Glycoproteins, Phosphoproteins, Proto-Oncogene Proteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors, Transcription Factor RelB, Transcription Factors
@article{nicolas_vivo_1998,
title = {In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila},
author = {E Nicolas and Jean-Marc Reichhart and Jules A Hoffmann and Bruno Lemaitre},
issn = {0021-9258},
year = {1998},
date = {1998-04-01},
journal = {J. Biol. Chem.},
volume = {273},
number = {17},
pages = {10463--10469},
abstract = {The dorsoventral regulatory gene pathway (spätzle/Toll/cactus) controls the expression of several antimicrobial genes during the immune response of Drosophila. This regulatory cascade shows striking similarities with the cytokine-induced activation cascade of NF-kappaB during the inflammatory response in mammals. Here, we have studied the regulation of the IkappaB homologue Cactus in the fat body during the immune response. We observe that the cactus gene is up-regulated in response to immune challenge. Interestingly, the expression of the cactus gene is controlled by the spätzle/Toll/cactus gene pathway, indicating that the cactus gene is autoregulated. We also show that two Cactus isoforms are expressed in the cytoplasm of fat body cells and that they are rapidly degraded and resynthesized after immune challenge. This degradation is also dependent on the Toll signaling pathway. Altogether, our results underline the striking similarities between the regulation of IkappaB and cactus during the immune response.},
keywords = {Animals, Cell Surface, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, Insect Proteins, Larva, M3i, Membrane Glycoproteins, Phosphoproteins, Proto-Oncogene Proteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors, Transcription Factor RelB, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
The dorsoventral regulatory gene pathway (spätzle/Toll/cactus) controls the expression of several antimicrobial genes during the immune response of Drosophila. This regulatory cascade shows striking similarities with the cytokine-induced activation cascade of NF-kappaB during the inflammatory response in mammals. Here, we have studied the regulation of the IkappaB homologue Cactus in the fat body during the immune response. We observe that the cactus gene is up-regulated in response to immune challenge. Interestingly, the expression of the cactus gene is controlled by the spätzle/Toll/cactus gene pathway, indicating that the cactus gene is autoregulated. We also show that two Cactus isoforms are expressed in the cytoplasm of fat body cells and that they are rapidly degraded and resynthesized after immune challenge. This degradation is also dependent on the Toll signaling pathway. Altogether, our results underline the striking similarities between the regulation of IkappaB and cactus during the immune response.
Reichhart Jean-Marc, Ferrandon Dominique
Green Balancers. Article de journal
Dans: D. I. S., vol. 81, p. 201–202, 1998.
Résumé | BibTeX | Étiquettes: ferrandon, M3i, reichhart
@article{reichhart_green_1998,
title = {Green Balancers.},
author = {Jean-Marc Reichhart and Dominique Ferrandon},
year = {1998},
date = {1998-01-01},
journal = {D. I. S.},
volume = {81},
pages = {201--202},
abstract = {We have used the S65T green fluorescent protein (GFP ; (Chalfie et al., 1994) ; (Heim et al., 1995)) as a vital reporter to introduce a dominant innocuous marker onto the balancers of the three major chromosomes of D. melanogaster.},
keywords = {ferrandon, M3i, reichhart},
pubstate = {published},
tppubtype = {article}
}
We have used the S65T green fluorescent protein (GFP ; (Chalfie et al., 1994) ; (Heim et al., 1995)) as a vital reporter to introduce a dominant innocuous marker onto the balancers of the three major chromosomes of D. melanogaster.
1997
Lemaitre Bruno, Reichhart Jean-Marc, Hoffmann Jules A
Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms Article de journal
Dans: Proc. Natl. Acad. Sci. U.S.A., vol. 94, no. 26, p. 14614–14619, 1997, ISSN: 0027-8424.
Résumé | BibTeX | Étiquettes: Animals, Genes, hoffmann, Immunity, Insect, M3i, Peptides, reichhart
@article{lemaitre_drosophila_1997,
title = {Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms},
author = {Bruno Lemaitre and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {0027-8424},
year = {1997},
date = {1997-12-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {94},
number = {26},
pages = {14614--14619},
abstract = {Insects respond to microbial infection by the rapid and transient expression of several genes encoding potent antimicrobial peptides. Herein we demonstrate that this antimicrobial response of Drosophila is not aspecific but can discriminate between various classes of microorganisms. We first observe that the genes encoding antibacterial and antifungal peptides are differentially expressed after injection of distinct microorganisms. More strikingly, Drosophila that are naturally infected by entomopathogenic fungi exhibit an adapted response by producing only peptides with antifungal activities. This response is mediated through the selective activation of the Toll pathway.},
keywords = {Animals, Genes, hoffmann, Immunity, Insect, M3i, Peptides, reichhart},
pubstate = {published},
tppubtype = {article}
}
Insects respond to microbial infection by the rapid and transient expression of several genes encoding potent antimicrobial peptides. Herein we demonstrate that this antimicrobial response of Drosophila is not aspecific but can discriminate between various classes of microorganisms. We first observe that the genes encoding antibacterial and antifungal peptides are differentially expressed after injection of distinct microorganisms. More strikingly, Drosophila that are naturally infected by entomopathogenic fungi exhibit an adapted response by producing only peptides with antifungal activities. This response is mediated through the selective activation of the Toll pathway.
Hoffmann Jules A, Reichhart Jean-Marc
Drosophila immunity. Article de journal
Dans: Trends in Cell Biology, vol. 7, p. 309–316, 1997.
Résumé | BibTeX | Étiquettes: hoffmann, M3i, reichhart
@article{hoffmann_drosophila_1997,
title = {Drosophila immunity.},
author = {Jules A Hoffmann and Jean-Marc Reichhart},
year = {1997},
date = {1997-01-01},
journal = {Trends in Cell Biology},
volume = {7},
pages = {309--316},
abstract = {Septic injury induces in Drosophila the rapid and transient transcription of several genes encoding potent antimicrobial peptides. Significant structural and functional similarities exist between the injury-induced signalling cascades leading to antimicrobial peptide gene expression in Drosophila and cytokine-induced expression of mammalian acute-phase proteins. Here, the authors discuss their understanding of these pathways and their relationships to those found in the mammalian cells. They also analyse non-self recognition and the role of blood cells in Drosophila host defence.},
keywords = {hoffmann, M3i, reichhart},
pubstate = {published},
tppubtype = {article}
}
Septic injury induces in Drosophila the rapid and transient transcription of several genes encoding potent antimicrobial peptides. Significant structural and functional similarities exist between the injury-induced signalling cascades leading to antimicrobial peptide gene expression in Drosophila and cytokine-induced expression of mammalian acute-phase proteins. Here, the authors discuss their understanding of these pathways and their relationships to those found in the mammalian cells. They also analyse non-self recognition and the role of blood cells in Drosophila host defence.
1996
Gross I, Georgel Philippe, Kappler Christine, Reichhart Jean-Marc, Hoffmann Jules A
Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin Article de journal
Dans: Nucleic Acids Res., vol. 24, no. 7, p. 1238–1245, 1996, ISSN: 0305-1048.
Résumé | BibTeX | Étiquettes: Animals, Antimicrobial Cationic Peptides, Base Sequence, DNA Primers, DNA-Binding Proteins, Gene Expression Regulation, Genetic, hoffmann, Insect Hormones, Insect Proteins, M3i, NF-kappa B, Nuclear Proteins, Peptides, Phosphoproteins, reichhart, Transcription, Transcription Factors, Transcriptional Activation
@article{gross_drosophila_1996,
title = {Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin},
author = {I Gross and Philippe Georgel and Christine Kappler and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {0305-1048},
year = {1996},
date = {1996-04-01},
journal = {Nucleic Acids Res.},
volume = {24},
number = {7},
pages = {1238--1245},
abstract = {In Drosophila, bacterial challenge induces the rapid transcription of several genes encoding potent antibacterial peptides. The upstream sequences of the diptericin and cecropin Al genes, which have been investigated in detail, contain two, respectively one sequence element homologous to the binding site of the mammalian nuclear factor kappaB. These elements have been shown to be mandatory for immune-induced transcription of both genes. Functional studies have shown that these kappaB-related elements can be the target for the Drosophila Rel proteins dorsal and Dif. Here we present a comparative analysis of the transactivating capacities of these proteins on reporter genes fused to either the diptericin or the cecropin kappaB-related motifs. We conclude from our results: (i) the kappaB motifs of the diptericin and cecropin genes are not functionally equivalent; (ii) the dorsal and Dif proteins have distinct DNA-binding characteristics; (iii) dorsal and Dif can heterodimerize in vitro; (iv) mutants containing no copies of dorsal and a single copy of Dif retain their full capacity to express the diptericin and cecropin genes in response to challenge.},
keywords = {Animals, Antimicrobial Cationic Peptides, Base Sequence, DNA Primers, DNA-Binding Proteins, Gene Expression Regulation, Genetic, hoffmann, Insect Hormones, Insect Proteins, M3i, NF-kappa B, Nuclear Proteins, Peptides, Phosphoproteins, reichhart, Transcription, Transcription Factors, Transcriptional Activation},
pubstate = {published},
tppubtype = {article}
}
In Drosophila, bacterial challenge induces the rapid transcription of several genes encoding potent antibacterial peptides. The upstream sequences of the diptericin and cecropin Al genes, which have been investigated in detail, contain two, respectively one sequence element homologous to the binding site of the mammalian nuclear factor kappaB. These elements have been shown to be mandatory for immune-induced transcription of both genes. Functional studies have shown that these kappaB-related elements can be the target for the Drosophila Rel proteins dorsal and Dif. Here we present a comparative analysis of the transactivating capacities of these proteins on reporter genes fused to either the diptericin or the cecropin kappaB-related motifs. We conclude from our results: (i) the kappaB motifs of the diptericin and cecropin genes are not functionally equivalent; (ii) the dorsal and Dif proteins have distinct DNA-binding characteristics; (iii) dorsal and Dif can heterodimerize in vitro; (iv) mutants containing no copies of dorsal and a single copy of Dif retain their full capacity to express the diptericin and cecropin genes in response to challenge.
Hoffmann Jules A, Reichhart Jean-Marc, Hetru Charles
Innate immunity in higher insects Article de journal
Dans: Curr. Opin. Immunol., vol. 8, no. 1, p. 8–13, 1996, ISSN: 0952-7915.
Résumé | BibTeX | Étiquettes: Animals, Base Sequence, Cyclic, hoffmann, Immunity, Immunologic, Immunological, Innate, insects, M3i, Models, Peptide Hydrolases, Peptides, Receptors, reichhart
@article{hoffmann_innate_1996,
title = {Innate immunity in higher insects},
author = {Jules A Hoffmann and Jean-Marc Reichhart and Charles Hetru},
issn = {0952-7915},
year = {1996},
date = {1996-02-01},
journal = {Curr. Opin. Immunol.},
volume = {8},
number = {1},
pages = {8--13},
abstract = {The hallmark of the innate immune response of higher insects is the rapid and transient synthesis of a battery of broad spectrum antimicrobial peptides by the fat body. The control of the genes encoding these peptides involves cis-regulatory promoter elements homologous to sequences functional in mammalian acute-phase genes. Study of immune-deficient mutants of Drosophila has indicated that distinct pathways control the antibacterial and antifungal responses in this species. Novel receptors potentially involved in the initiation of the immune response have been recently characterized.},
keywords = {Animals, Base Sequence, Cyclic, hoffmann, Immunity, Immunologic, Immunological, Innate, insects, M3i, Models, Peptide Hydrolases, Peptides, Receptors, reichhart},
pubstate = {published},
tppubtype = {article}
}
The hallmark of the innate immune response of higher insects is the rapid and transient synthesis of a battery of broad spectrum antimicrobial peptides by the fat body. The control of the genes encoding these peptides involves cis-regulatory promoter elements homologous to sequences functional in mammalian acute-phase genes. Study of immune-deficient mutants of Drosophila has indicated that distinct pathways control the antibacterial and antifungal responses in this species. Novel receptors potentially involved in the initiation of the immune response have been recently characterized.
Charlet Maurice, Lagueux Marie, Reichhart Jean-Marc, Hoffmann Danièle, Braun A, Meister Marie
Cloning of the gene encoding the antibacterial peptide drosocin involved in Drosophila immunity. Expression studies during the immune response. Article de journal
Dans: Eur. J. Biochem., vol. 241, p. 699–706, 1996.
Résumé | BibTeX | Étiquettes: M3i, reichhart
@article{charlet_cloning_1996,
title = {Cloning of the gene encoding the antibacterial peptide drosocin involved in Drosophila immunity. Expression studies during the immune response.},
author = {Maurice Charlet and Marie Lagueux and Jean-Marc Reichhart and Danièle Hoffmann and A Braun and Marie Meister},
year = {1996},
date = {1996-01-01},
journal = {Eur. J. Biochem.},
volume = {241},
pages = {699--706},
abstract = {A potent inducible antibacterial peptide carrying an O-glycosylated substitution has recently been isolated from Drosophila [Bulet et al. (1993) J. Biol. Chem. 268 14893-14897]. Here we report cloning studies that show that Drosophila contains a single, intronless gene, located at position 51C1-6, which encodes the precursor protein from which drosocin is processed. The upstream and the downstream sequences of the drosocin gene contain putative cis-regulatory elements similar to mammalian regulatory motifs, namely three kB-related decameric sequences. The drosocin gene is silent in naive animals, and is strongly induced with acute phase kinetics after immune challenge in larvae and adults. We have established several transgenic fly lines in which reporter genes were placed under the control of various drosocin promoter sequences. Our results indcate that 2.5 kb of upstream sequences confer inducibility and tissue specificity to the transgene, but that the level of its expression in the fat body after immune challenge},
keywords = {M3i, reichhart},
pubstate = {published},
tppubtype = {article}
}
A potent inducible antibacterial peptide carrying an O-glycosylated substitution has recently been isolated from Drosophila [Bulet et al. (1993) J. Biol. Chem. 268 14893-14897]. Here we report cloning studies that show that Drosophila contains a single, intronless gene, located at position 51C1-6, which encodes the precursor protein from which drosocin is processed. The upstream and the downstream sequences of the drosocin gene contain putative cis-regulatory elements similar to mammalian regulatory motifs, namely three kB-related decameric sequences. The drosocin gene is silent in naive animals, and is strongly induced with acute phase kinetics after immune challenge in larvae and adults. We have established several transgenic fly lines in which reporter genes were placed under the control of various drosocin promoter sequences. Our results indcate that 2.5 kb of upstream sequences confer inducibility and tissue specificity to the transgene, but that the level of its expression in the fat body after immune challenge
Michaut Lydia, Fehlbaum P, Moniatte M, Dorsselaer Van A, Reichhart Jean-Marc, Bulet Philippe
Determination of the disulfide array of the first inducible antifungal peptide from insects : drosomycin from Drosophila melanogaster. Article de journal
Dans: FEBS Lett., vol. 395, p. 6–10, 1996.
Résumé | BibTeX | Étiquettes: M3i, reichhart
@article{michaut_determination_1996,
title = {Determination of the disulfide array of the first inducible antifungal peptide from insects : drosomycin from Drosophila melanogaster.},
author = {Lydia Michaut and P Fehlbaum and M Moniatte and Van A Dorsselaer and Jean-Marc Reichhart and Philippe Bulet},
year = {1996},
date = {1996-01-01},
journal = {FEBS Lett.},
volume = {395},
pages = {6--10},
abstract = {Drosomycin is a 44-residue antifungal peptide with four intramolecular disulfide bridges which have been isolated from immune-challenged Drosophila. To produce adequate amounts of this peptide for 3D-structure analysis, studies on the mode of action and activity spectrum, we expressed a synthetic cDNA in Saccharomyces cerevisiae. For this purpose, we used the mating factor a gene and concomitantly over-expressed the KEX2 gene to increase the yield of fully processed drosomycin. Using a combination of Edman degradation and mass spectrometry, we show that drosomycin shares the same array of intramolecular disulfide bridges than plant defensins, in addition to their sequence similarities.},
keywords = {M3i, reichhart},
pubstate = {published},
tppubtype = {article}
}
Drosomycin is a 44-residue antifungal peptide with four intramolecular disulfide bridges which have been isolated from immune-challenged Drosophila. To produce adequate amounts of this peptide for 3D-structure analysis, studies on the mode of action and activity spectrum, we expressed a synthetic cDNA in Saccharomyces cerevisiae. For this purpose, we used the mating factor a gene and concomitantly over-expressed the KEX2 gene to increase the yield of fully processed drosomycin. Using a combination of Edman degradation and mass spectrometry, we show that drosomycin shares the same array of intramolecular disulfide bridges than plant defensins, in addition to their sequence similarities.
Lemaitre Bruno, Nicolas E, Michaut Lydia, Reichhart Jean-Marc, Hoffmann Jules A
The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults Article de journal
Dans: Cell, vol. 86, no. 6, p. 973–983, 1996, ISSN: 0092-8674.
Résumé | BibTeX | Étiquettes: Animals, Antifungal Agents, Cell Surface, DNA-Binding Proteins, Fungi, Gene Expression, Genes, hoffmann, Insect, Insect Hormones, Insect Proteins, M3i, Membrane Glycoproteins, MHC Class II, Mutation, Mycoses, NF-kappa B, Phosphoproteins, Proteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors
@article{lemaitre_dorsoventral_1996,
title = {The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults},
author = {Bruno Lemaitre and E Nicolas and Lydia Michaut and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {0092-8674},
year = {1996},
date = {1996-01-01},
journal = {Cell},
volume = {86},
number = {6},
pages = {973--983},
abstract = {The cytokine-induced activation cascade of NF-kappaB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB). Here we demonstrate that these parallels extend to the immune response of Drosophila. In particular, the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults. We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways.},
keywords = {Animals, Antifungal Agents, Cell Surface, DNA-Binding Proteins, Fungi, Gene Expression, Genes, hoffmann, Insect, Insect Hormones, Insect Proteins, M3i, Membrane Glycoproteins, MHC Class II, Mutation, Mycoses, NF-kappa B, Phosphoproteins, Proteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
The cytokine-induced activation cascade of NF-kappaB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB). Here we demonstrate that these parallels extend to the immune response of Drosophila. In particular, the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults. We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways.
1995
Lemaitre Bruno, Kromer-Metzger E, Michaut Lydia, Nicolas E, Meister Marie, Georgel Philippe, Reichhart Jean-Marc, Hoffmann Jules A
A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense Article de journal
Dans: Proc. Natl. Acad. Sci. U.S.A., vol. 92, no. 21, p. 9465–9469, 1995, ISSN: 0027-8424.
Résumé | BibTeX | Étiquettes: Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Bacterial Infections, Base Sequence, Gene Expression Regulation, Genes, Glycopeptides, hoffmann, Insect, Insect Hormones, Insect Proteins, M3i, Male, Mutation, Mycoses, Nucleic Acid, Peptides, Protein Binding, Recessive, Regulatory Sequences, reichhart, Reporter, Survival Analysis
@article{lemaitre_recessive_1995,
title = {A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense},
author = {Bruno Lemaitre and E Kromer-Metzger and Lydia Michaut and E Nicolas and Marie Meister and Philippe Georgel and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {0027-8424},
year = {1995},
date = {1995-10-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {92},
number = {21},
pages = {9465--9469},
abstract = {In this paper we report a recessive mutation, immune deficiency (imd), that impairs the inducibility of all genes encoding antibacterial peptides during the immune response of Drosophila. When challenged with bacteria, flies carrying this mutation show a lower survival rate than wild-type flies. We also report that, in contrast to the antibacterial peptides, the antifungal peptide drosomycin remains inducible in a homozygous imd mutant background. These results point to the existence of two different pathways leading to the expression of two types of target genes, encoding either the antibacterial peptides or the antifungal peptide drosomycin.},
keywords = {Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Bacterial Infections, Base Sequence, Gene Expression Regulation, Genes, Glycopeptides, hoffmann, Insect, Insect Hormones, Insect Proteins, M3i, Male, Mutation, Mycoses, Nucleic Acid, Peptides, Protein Binding, Recessive, Regulatory Sequences, reichhart, Reporter, Survival Analysis},
pubstate = {published},
tppubtype = {article}
}
In this paper we report a recessive mutation, immune deficiency (imd), that impairs the inducibility of all genes encoding antibacterial peptides during the immune response of Drosophila. When challenged with bacteria, flies carrying this mutation show a lower survival rate than wild-type flies. We also report that, in contrast to the antibacterial peptides, the antifungal peptide drosomycin remains inducible in a homozygous imd mutant background. These results point to the existence of two different pathways leading to the expression of two types of target genes, encoding either the antibacterial peptides or the antifungal peptide drosomycin.
Levashina Elena A, Ohresser S, Bulet Philippe, Reichhart Jean-Marc, Hetru Charles, Hoffmann Jules A
Metchnikowin, a novel immune-inducible proline-rich peptide from Drosophila with antibacterial and antifungal properties Article de journal
Dans: Eur. J. Biochem., vol. 233, no. 2, p. 694–700, 1995, ISSN: 0014-2956.
Résumé | BibTeX | Étiquettes: Animals, Anti-Bacterial Agents, Antifungal Agents, Antimicrobial Cationic Peptides, bacteria, Base Sequence, Cells, Chromosome Mapping, Cloning, Cultured, Genetic, hoffmann, M3i, Molecular, Peptides, Proline, reichhart, Transcription
@article{levashina_metchnikowin_1995,
title = {Metchnikowin, a novel immune-inducible proline-rich peptide from Drosophila with antibacterial and antifungal properties},
author = {Elena A Levashina and S Ohresser and Philippe Bulet and Jean-Marc Reichhart and Charles Hetru and Jules A Hoffmann},
issn = {0014-2956},
year = {1995},
date = {1995-10-01},
journal = {Eur. J. Biochem.},
volume = {233},
number = {2},
pages = {694--700},
abstract = {One of the characteristics of the host defense of higher insects is the rapid and transient synthesis of a variety of potent antimicrobial peptides. To date, several distinct inducible antimicrobial peptides or peptide families have been totally or partially characterized. We present here the isolation and characterization of a novel 26-residue proline-rich immune-inducible peptide from Drosophila, which exhibits both antibacterial (Gram-positive) and antifungal activities. Peptide sequencing and cDNA cloning indicate the presense of two isoforms in our Drosophila Oregon strain, which differ by one residue (His compared to Arg) as a consequence of a single nucleotide change. The gene, which maps in position 52A1-2 on the right arm of the second chromosome, is expressed in the fat body after immune challenge. The novel peptide, which we propose to name metchnikowin, is a member of a family of proline-rich peptides, and we discuss the possible evolutionary relationships within this family.},
keywords = {Animals, Anti-Bacterial Agents, Antifungal Agents, Antimicrobial Cationic Peptides, bacteria, Base Sequence, Cells, Chromosome Mapping, Cloning, Cultured, Genetic, hoffmann, M3i, Molecular, Peptides, Proline, reichhart, Transcription},
pubstate = {published},
tppubtype = {article}
}
One of the characteristics of the host defense of higher insects is the rapid and transient synthesis of a variety of potent antimicrobial peptides. To date, several distinct inducible antimicrobial peptides or peptide families have been totally or partially characterized. We present here the isolation and characterization of a novel 26-residue proline-rich immune-inducible peptide from Drosophila, which exhibits both antibacterial (Gram-positive) and antifungal activities. Peptide sequencing and cDNA cloning indicate the presense of two isoforms in our Drosophila Oregon strain, which differ by one residue (His compared to Arg) as a consequence of a single nucleotide change. The gene, which maps in position 52A1-2 on the right arm of the second chromosome, is expressed in the fat body after immune challenge. The novel peptide, which we propose to name metchnikowin, is a member of a family of proline-rich peptides, and we discuss the possible evolutionary relationships within this family.
Georgel Philippe, Kappler Christine, Langley E, Gross I, Nicolas E, Reichhart Jean-Marc, Hoffmann Jules A
Drosophila immunity. A sequence homologous to mammalian interferon consensus response element enhances the activity of the diptericin promoter Article de journal
Dans: Nucleic Acids Res., vol. 23, no. 7, p. 1140–1145, 1995, ISSN: 0305-1048.
Résumé | BibTeX | Étiquettes: Animals, Base Sequence, CCAAT-Enhancer-Binding Proteins, DNA, DNA-Binding Proteins, Genes, Genetic, hoffmann, Immunity, Insect, Insect Hormones, Insect Proteins, interferons, Lipopolysaccharides, M3i, NF-kappa B, Nuclear Proteins, Plasmids, Promoter Regions, reichhart, Up-Regulation
@article{georgel_drosophila_1995,
title = {Drosophila immunity. A sequence homologous to mammalian interferon consensus response element enhances the activity of the diptericin promoter},
author = {Philippe Georgel and Christine Kappler and E Langley and I Gross and E Nicolas and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {0305-1048},
year = {1995},
date = {1995-04-01},
journal = {Nucleic Acids Res.},
volume = {23},
number = {7},
pages = {1140--1145},
abstract = {Bacterial challenge of larvae or adults of Drosophila induces the rapid transcription of several genes encoding antibacterial peptides with a large spectrum of activity. One of these peptides, the 82-residue anti-gram negative diptericin, is encoded by a single intronless gene and we are investigating the control of expression of this gene. Previous studies using both transgenic experiments and footprint analysis have highlighted the role in the induction of this gene of a 30 nucleotide region which contains three partially overlapping motifs with sequence homology to mammalian NF-kappa B and NF-IL6 response elements and to the GAAANN sequence present in the interferon consensus response elements of some mammalian interferon-induced genes. We now show that the latter sequence binds in immune responsive tissues (fat body, blood cells) of Drosophila a approximately 45 kDa polypeptide which cross-reacts with a polyserum directed against mammalian interferon Regulatory Factor-I. Using a transfection assay of Drosophila tumorous blood cells, we show that the GAAANN sequence positively regulates the activity of the diptericin promoter. We propose that this motif cooperatively interacts with the other response elements in the regulation of the diptericin gene expression.},
keywords = {Animals, Base Sequence, CCAAT-Enhancer-Binding Proteins, DNA, DNA-Binding Proteins, Genes, Genetic, hoffmann, Immunity, Insect, Insect Hormones, Insect Proteins, interferons, Lipopolysaccharides, M3i, NF-kappa B, Nuclear Proteins, Plasmids, Promoter Regions, reichhart, Up-Regulation},
pubstate = {published},
tppubtype = {article}
}
Bacterial challenge of larvae or adults of Drosophila induces the rapid transcription of several genes encoding antibacterial peptides with a large spectrum of activity. One of these peptides, the 82-residue anti-gram negative diptericin, is encoded by a single intronless gene and we are investigating the control of expression of this gene. Previous studies using both transgenic experiments and footprint analysis have highlighted the role in the induction of this gene of a 30 nucleotide region which contains three partially overlapping motifs with sequence homology to mammalian NF-kappa B and NF-IL6 response elements and to the GAAANN sequence present in the interferon consensus response elements of some mammalian interferon-induced genes. We now show that the latter sequence binds in immune responsive tissues (fat body, blood cells) of Drosophila a approximately 45 kDa polypeptide which cross-reacts with a polyserum directed against mammalian interferon Regulatory Factor-I. Using a transfection assay of Drosophila tumorous blood cells, we show that the GAAANN sequence positively regulates the activity of the diptericin promoter. We propose that this motif cooperatively interacts with the other response elements in the regulation of the diptericin gene expression.
Lemaitre Bruno, Meister Marie, Govind S, Georgel Philippe, Steward R, Reichhart Jean-Marc, Hoffmann Jules A
Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila Article de journal
Dans: EMBO J., vol. 14, no. 3, p. 536–545, 1995, ISSN: 0261-4189.
Résumé | BibTeX | Étiquettes: Animals, Anti-Bacterial Agents, Anti-Infective Agents, Antimicrobial Cationic Peptides, Biological Transport, Cell Nucleus, Cell Surface, DNA-Binding Proteins, Fat Body, Gene Expression Regulation, Genetic, hoffmann, Immunity, Immunohistochemistry, Insect Hormones, Insect Proteins, M3i, Melanins, Membrane Glycoproteins, Mutation, Neoplasms, Nuclear Proteins, Phosphoproteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors, Transcription, Transcription Factors
@article{lemaitre_functional_1995,
title = {Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila},
author = {Bruno Lemaitre and Marie Meister and S Govind and Philippe Georgel and R Steward and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {0261-4189},
year = {1995},
date = {1995-01-01},
journal = {EMBO J.},
volume = {14},
number = {3},
pages = {536--545},
abstract = {In addition to its function in embryonic development, the NF-kappa B/rel-related gene dorsal (dl) of Drosophila is expressed in larval and adult fat body where its RNA expression is enhanced upon injury. Injury also leads to a rapid nuclear translocation of dl from the cytoplasm in fat body cells. Here we present data which strongly suggest that the nuclear localization of dl during the immune response is controlled by the Toll signaling pathway, comprising gene products that participate in the intracellular part of the embryonic dorsoventral pathway. We also report that in mutants such as Toll or cactus, which exhibit melanotic tumor phenotypes, dl is constitutively nuclear. Together, these results point to a potential link between the Toll signaling pathway and melanotic tumor induction. Although dl has been shown previously to bind to kappa B-related motifs within the promoter of the antibacterial peptide coding gene diptericin, we find that injury-induced expression of diptericin can occur in the absence of dl. Furthermore, the melanotic tumor phenotype of Toll and cactus is not dl dependent. These data underline the complexity of the Drosophila immune response. Finally, we observed that like other rel proteins, dl can control the level of its own transcription.},
keywords = {Animals, Anti-Bacterial Agents, Anti-Infective Agents, Antimicrobial Cationic Peptides, Biological Transport, Cell Nucleus, Cell Surface, DNA-Binding Proteins, Fat Body, Gene Expression Regulation, Genetic, hoffmann, Immunity, Immunohistochemistry, Insect Hormones, Insect Proteins, M3i, Melanins, Membrane Glycoproteins, Mutation, Neoplasms, Nuclear Proteins, Phosphoproteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors, Transcription, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
In addition to its function in embryonic development, the NF-kappa B/rel-related gene dorsal (dl) of Drosophila is expressed in larval and adult fat body where its RNA expression is enhanced upon injury. Injury also leads to a rapid nuclear translocation of dl from the cytoplasm in fat body cells. Here we present data which strongly suggest that the nuclear localization of dl during the immune response is controlled by the Toll signaling pathway, comprising gene products that participate in the intracellular part of the embryonic dorsoventral pathway. We also report that in mutants such as Toll or cactus, which exhibit melanotic tumor phenotypes, dl is constitutively nuclear. Together, these results point to a potential link between the Toll signaling pathway and melanotic tumor induction. Although dl has been shown previously to bind to kappa B-related motifs within the promoter of the antibacterial peptide coding gene diptericin, we find that injury-induced expression of diptericin can occur in the absence of dl. Furthermore, the melanotic tumor phenotype of Toll and cactus is not dl dependent. These data underline the complexity of the Drosophila immune response. Finally, we observed that like other rel proteins, dl can control the level of its own transcription.
1994
Meister Marie, Braun A, Kappler Christine, Reichhart Jean-Marc, Hoffmann Jules A
Insect immunity. A transgenic analysis in Drosophila defines several functional domains in the diptericin promoter Article de journal
Dans: EMBO J., vol. 13, no. 24, p. 5958–5966, 1994, ISSN: 0261-4189.
Résumé | BibTeX | Étiquettes: Animals, Anti-Infective Agents, Base Sequence, beta-Galactosidase, DNA Mutational Analysis, Female, Gene Expression Regulation, Genetic, Genetically Modified, Germ Cells, hoffmann, Insect Hormones, Insect Proteins, M3i, Male, Models, Nucleic Acid, Promoter Regions, Recombinant Fusion Proteins, reichhart, Repetitive Sequences, Transformation
@article{meister_insect_1994,
title = {Insect immunity. A transgenic analysis in Drosophila defines several functional domains in the diptericin promoter},
author = {Marie Meister and A Braun and Christine Kappler and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {0261-4189},
year = {1994},
date = {1994-12-01},
journal = {EMBO J.},
volume = {13},
number = {24},
pages = {5958--5966},
abstract = {Diptericins are antibacterial polypeptides which are strongly induced in the fat body and blood cells of dipteran insects in response to septic injury. The promoter of the single-copy, intronless diptericin gene of Drosophila contains several nucleotide sequences homologous to mammalian cis-regulatory motifs involved in the control of acute phase response genes. Extending our previous studies on the expression of the diptericin gene, we now report a quantitative analysis of the contribution of various putative regulatory elements to the bacterial inducibility of this gene, based on the generation of 60 transgenic fly lines carrying different elements fused to a reporter gene. Our data definitively identify two Kappa B-related motifs in the proximal promoter as the sites conferring inducibility and tissue-specific expression to the diptericin gene. These motifs alone, however, mediate only minimal levels of expression. Additional proximal regulatory elements are necessary to attain some 20% of the full response and we suspect a role for sequences homologous to mammalian IL6 response elements and interferon-gamma responsive sites in this up-regulation. The transgenic experiments also reveal the existence of a distal regulatory element located upstream of -0.6 kb which increases the level of expression by a factor of five.},
keywords = {Animals, Anti-Infective Agents, Base Sequence, beta-Galactosidase, DNA Mutational Analysis, Female, Gene Expression Regulation, Genetic, Genetically Modified, Germ Cells, hoffmann, Insect Hormones, Insect Proteins, M3i, Male, Models, Nucleic Acid, Promoter Regions, Recombinant Fusion Proteins, reichhart, Repetitive Sequences, Transformation},
pubstate = {published},
tppubtype = {article}
}
Diptericins are antibacterial polypeptides which are strongly induced in the fat body and blood cells of dipteran insects in response to septic injury. The promoter of the single-copy, intronless diptericin gene of Drosophila contains several nucleotide sequences homologous to mammalian cis-regulatory motifs involved in the control of acute phase response genes. Extending our previous studies on the expression of the diptericin gene, we now report a quantitative analysis of the contribution of various putative regulatory elements to the bacterial inducibility of this gene, based on the generation of 60 transgenic fly lines carrying different elements fused to a reporter gene. Our data definitively identify two Kappa B-related motifs in the proximal promoter as the sites conferring inducibility and tissue-specific expression to the diptericin gene. These motifs alone, however, mediate only minimal levels of expression. Additional proximal regulatory elements are necessary to attain some 20% of the full response and we suspect a role for sequences homologous to mammalian IL6 response elements and interferon-gamma responsive sites in this up-regulation. The transgenic experiments also reveal the existence of a distal regulatory element located upstream of -0.6 kb which increases the level of expression by a factor of five.
Dimarcq Jean-Luc, Hoffmann Danièle, Meister Marie, Bulet Philippe, Lanot R, Reichhart Jean-Marc, Hoffmann Jules A
Characterization and transcriptional profiles of a Drosophila gene encoding an insect defensin. A study in insect immunity Article de journal
Dans: Eur. J. Biochem., vol. 221, no. 1, p. 201–209, 1994, ISSN: 0014-2956.
Résumé | BibTeX | Étiquettes: Animals, Base Sequence, Blood Proteins, Chromosome Mapping, Cloning, Complementary, Defensins, DNA, Gene Expression, Genetic, Gram-Positive Bacteria, hoffmann, Larva, M3i, Molecular, Molecular Structure, Nucleic Acid, Protein Precursors, Regulatory Sequences, reichhart, Transcription
@article{dimarcq_characterization_1994,
title = {Characterization and transcriptional profiles of a Drosophila gene encoding an insect defensin. A study in insect immunity},
author = {Jean-Luc Dimarcq and Danièle Hoffmann and Marie Meister and Philippe Bulet and R Lanot and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {0014-2956},
year = {1994},
date = {1994-04-01},
journal = {Eur. J. Biochem.},
volume = {221},
number = {1},
pages = {201--209},
abstract = {Insect defensins are a family of 4-kDa, cationic, inducible antibacterial peptides which bear six cysteine residues engaged in three intramolecular disulfide bridges. They owe their name to certain sequence similarities with defensins from mammalian neutrophiles and macrophages. We report the characterization of a novel defensin isoform from Drosophila and the cloning of the gene encoding a preprodefensin. The gene, which is intronless and present in a single copy/haploid genome, maps at position 46CD on the right arm of the second chromosome. The analysis of the upstream region of the gene reveals the presence of multiple putative cis-regulatory sequences similar to mammalian regulatory motifs of acute-phase-response genes. Transcriptional profiles indicate that the Drosophila defensin gene is induced by bacterial challenge with acute-phase kinetics. It is also expressed in the absence of immune challenge during metamorphosis. These and other data on the Drosophila defensin gene lead us to suggest that insect and mammalian defensins have evolved independently.},
keywords = {Animals, Base Sequence, Blood Proteins, Chromosome Mapping, Cloning, Complementary, Defensins, DNA, Gene Expression, Genetic, Gram-Positive Bacteria, hoffmann, Larva, M3i, Molecular, Molecular Structure, Nucleic Acid, Protein Precursors, Regulatory Sequences, reichhart, Transcription},
pubstate = {published},
tppubtype = {article}
}
Insect defensins are a family of 4-kDa, cationic, inducible antibacterial peptides which bear six cysteine residues engaged in three intramolecular disulfide bridges. They owe their name to certain sequence similarities with defensins from mammalian neutrophiles and macrophages. We report the characterization of a novel defensin isoform from Drosophila and the cloning of the gene encoding a preprodefensin. The gene, which is intronless and present in a single copy/haploid genome, maps at position 46CD on the right arm of the second chromosome. The analysis of the upstream region of the gene reveals the presence of multiple putative cis-regulatory sequences similar to mammalian regulatory motifs of acute-phase-response genes. Transcriptional profiles indicate that the Drosophila defensin gene is induced by bacterial challenge with acute-phase kinetics. It is also expressed in the absence of immune challenge during metamorphosis. These and other data on the Drosophila defensin gene lead us to suggest that insect and mammalian defensins have evolved independently.
Meister Marie, Georgel Philippe, Lemaitre Bruno, Kappler Christine, Lagueux Marie, Reichhart Jean-Marc, Hoffmann Jules A
Immune Gene Expression in Drosophila Book Section
Dans: Phylogenetic Perspectives in Immunity : The Insect Host Defense,, Hoffmann JA, Janeway Jr CA, Natori S., Austin, Georgetown, 1994.
BibTeX | Étiquettes: hoffmann, M3i, reichhart
@incollection{meister_immune_1994,
title = {Immune Gene Expression in Drosophila},
author = {Marie Meister and Philippe Georgel and Bruno Lemaitre and Christine Kappler and Marie Lagueux and Jean-Marc Reichhart and Jules A Hoffmann},
year = {1994},
date = {1994-01-01},
booktitle = {Phylogenetic Perspectives in Immunity : The Insect Host Defense,},
publisher = {Hoffmann JA, Janeway Jr CA, Natori S.},
address = {Austin, Georgetown},
edition = {R.G. Landes Company},
keywords = {hoffmann, M3i, reichhart},
pubstate = {published},
tppubtype = {incollection}
}
1993
Georgel Philippe, Meister Marie, Kappler Christine, Lemaitre Bruno, Reichhart Jean-Marc, Hoffmann Jules A
Insect immunity: the diptericin promoter contains multiple functional regulatory sequences homologous to mammalian acute-phase response elements Article de journal
Dans: Biochem. Biophys. Res. Commun., vol. 197, no. 2, p. 508–517, 1993, ISSN: 0006-291X.
Résumé | Liens | BibTeX | Étiquettes: Acute-Phase Proteins, Animals, Anti-Infective Agents, Base Sequence, Cell Line, Deoxyribonuclease I, DNA-Binding Proteins, Genetic, hoffmann, Insect Hormones, Insect Proteins, Larva, M3i, Mammals, NF-kappa B, Nucleic Acid, Oligonucleotide Probes, Polymerase Chain Reaction, Promoter Regions, Regulatory Sequences, reichhart
@article{georgel_insect_1993,
title = {Insect immunity: the diptericin promoter contains multiple functional regulatory sequences homologous to mammalian acute-phase response elements},
author = {Philippe Georgel and Marie Meister and Christine Kappler and Bruno Lemaitre and Jean-Marc Reichhart and Jules A Hoffmann},
doi = {10.1006/bbrc.1993.2508},
issn = {0006-291X},
year = {1993},
date = {1993-12-01},
journal = {Biochem. Biophys. Res. Commun.},
volume = {197},
number = {2},
pages = {508--517},
abstract = {We are using the diptericin gene as a model system to study the control of expression of the genes encoding antibacterial peptides during the Drosophila immune reaction. In order to investigate the putative regulatory regions in the diptericin promoter, we performed DNaseI footprinting experiments combined with gel-shift assays in two inducible systems: the larval fat body and a tumorous Drosophila blood cell line. Our results confirm the importance of kappa B-like elements previously described in the immune response of insects and reveal for the first time the involvement of other regions containing sequences homologous to mammalian acute-phase response elements.},
keywords = {Acute-Phase Proteins, Animals, Anti-Infective Agents, Base Sequence, Cell Line, Deoxyribonuclease I, DNA-Binding Proteins, Genetic, hoffmann, Insect Hormones, Insect Proteins, Larva, M3i, Mammals, NF-kappa B, Nucleic Acid, Oligonucleotide Probes, Polymerase Chain Reaction, Promoter Regions, Regulatory Sequences, reichhart},
pubstate = {published},
tppubtype = {article}
}
We are using the diptericin gene as a model system to study the control of expression of the genes encoding antibacterial peptides during the Drosophila immune reaction. In order to investigate the putative regulatory regions in the diptericin promoter, we performed DNaseI footprinting experiments combined with gel-shift assays in two inducible systems: the larval fat body and a tumorous Drosophila blood cell line. Our results confirm the importance of kappa B-like elements previously described in the immune response of insects and reveal for the first time the involvement of other regions containing sequences homologous to mammalian acute-phase response elements.
Hoffmann Jules A, Hetru Charles, Reichhart Jean-Marc
The humoral antibacterial response of Drosophila Article de journal
Dans: FEBS Lett., vol. 325, no. 1-2, p. 63–66, 1993, ISSN: 0014-5793.
Résumé | BibTeX | Étiquettes: Animals, Anti-Bacterial Agents, Base Sequence, Genes, hoffmann, Insect, Insect Hormones, Insect Proteins, M3i, reichhart, Sequence Homology
@article{hoffmann_humoral_1993,
title = {The humoral antibacterial response of Drosophila},
author = {Jules A Hoffmann and Charles Hetru and Jean-Marc Reichhart},
issn = {0014-5793},
year = {1993},
date = {1993-06-01},
journal = {FEBS Lett.},
volume = {325},
number = {1-2},
pages = {63--66},
abstract = {Drosophila, like other insects, responds to the injection of bacteria by the rapid and transient synthesis of a battery of potent antibacterial peptides. Only a few of these peptides have been fully characterized to date. We review our recent data on the control of the expression of a gene encoding one of the induced peptides, i.e. diptericin. Our data highlight the role of proximal cis-regulatory motifs similar to regulatory elements binding NF-kappa B and NF-IL6 in promoters of some immune genes of mammals. We argue that the Drosophila host defense is homologous to the mammalian acute phase response.},
keywords = {Animals, Anti-Bacterial Agents, Base Sequence, Genes, hoffmann, Insect, Insect Hormones, Insect Proteins, M3i, reichhart, Sequence Homology},
pubstate = {published},
tppubtype = {article}
}
Drosophila, like other insects, responds to the injection of bacteria by the rapid and transient synthesis of a battery of potent antibacterial peptides. Only a few of these peptides have been fully characterized to date. We review our recent data on the control of the expression of a gene encoding one of the induced peptides, i.e. diptericin. Our data highlight the role of proximal cis-regulatory motifs similar to regulatory elements binding NF-kappa B and NF-IL6 in promoters of some immune genes of mammals. We argue that the Drosophila host defense is homologous to the mammalian acute phase response.
Kappler Christine, Meister Marie, Lagueux Marie, Gateff E, Hoffmann Jules A, Reichhart Jean-Marc
Insect immunity. Two 17 bp repeats nesting a kappa B-related sequence confer inducibility to the diptericin gene and bind a polypeptide in bacteria-challenged Drosophila Article de journal
Dans: EMBO J., vol. 12, no. 4, p. 1561–1568, 1993, ISSN: 0261-4189.
Résumé | BibTeX | Étiquettes: Animals, Anti-Bacterial Agents, Base Sequence, Cloning, Gene Expression Regulation, Genes, Genetic, Genetically Modified, hoffmann, Insect, <