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I2CT
Immunologie, Immunopathologie et Chimie Thérapeutique
Publications
2002
Kambris Zakaria, Hoffmann Jules A, Imler Jean-Luc, Capovilla Maria
Tissue and stage-specific expression of the Tolls in Drosophila embryos Article de journal
Dans: Gene expression patterns: GEP, vol. 2, no. 3-4, p. 311–317, 2002, ISSN: 1567-133X.
Résumé | BibTeX | Étiquettes: Animals, Blotting, Cell Surface, Gene Expression Profiling, hoffmann, imler, Larva, M3i, Multigene Family, Northern, Receptors, Toll-Like Receptors
@article{kambris_tissue_2002,
title = {Tissue and stage-specific expression of the Tolls in Drosophila embryos},
author = {Zakaria Kambris and Jules A Hoffmann and Jean-Luc Imler and Maria Capovilla},
issn = {1567-133X},
year = {2002},
date = {2002-12-01},
journal = {Gene expression patterns: GEP},
volume = {2},
number = {3-4},
pages = {311--317},
abstract = {The Drosophila transmembrane receptor Toll plays a key role in specifying the dorsoventral axis of the embryo. At later stages of development, it controls the immune response of the fly to fungal and Gram-positive bacterial infections. The Drosophila genome has a total of nine Toll-like genes, including the previously characterized Toll (Toll-1) and 18-wheeler (Toll-2). Here we describe the embryonic expression patterns of the seven Toll-like genes Toll-3 through Toll-9. We find that these genes have distinct expression domains and that their expression is dynamically changing throughout embryonic development. This complex and tissue-specific regulation of Toll-like gene expression strongly suggests a role in embryonic development for most Drosophila Tolls. The evolving picture on the Toll family members in Drosophila contrasts with that of mammalian Toll-like receptors, which are predominantly expressed in immune responsive cells where their activation occurs via microbial structural determinants.},
keywords = {Animals, Blotting, Cell Surface, Gene Expression Profiling, hoffmann, imler, Larva, M3i, Multigene Family, Northern, Receptors, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
The Drosophila transmembrane receptor Toll plays a key role in specifying the dorsoventral axis of the embryo. At later stages of development, it controls the immune response of the fly to fungal and Gram-positive bacterial infections. The Drosophila genome has a total of nine Toll-like genes, including the previously characterized Toll (Toll-1) and 18-wheeler (Toll-2). Here we describe the embryonic expression patterns of the seven Toll-like genes Toll-3 through Toll-9. We find that these genes have distinct expression domains and that their expression is dynamically changing throughout embryonic development. This complex and tissue-specific regulation of Toll-like gene expression strongly suggests a role in embryonic development for most Drosophila Tolls. The evolving picture on the Toll family members in Drosophila contrasts with that of mammalian Toll-like receptors, which are predominantly expressed in immune responsive cells where their activation occurs via microbial structural determinants.
Duvic Bernard, Hoffmann Jules A, Meister Marie, Royet Julien
Notch signaling controls lineage specification during Drosophila larval hematopoiesis Article de journal
Dans: Curr. Biol., vol. 12, no. 22, p. 1923–1927, 2002, ISSN: 0960-9822.
Résumé | BibTeX | Étiquettes: Animals, Cell Differentiation, Hematopoiesis, hoffmann, Larva, Lymphoid Tissue, M3i, Membrane Proteins, Notch, Receptors, Signal Transduction
@article{duvic_notch_2002,
title = {Notch signaling controls lineage specification during Drosophila larval hematopoiesis},
author = {Bernard Duvic and Jules A Hoffmann and Marie Meister and Julien Royet},
issn = {0960-9822},
year = {2002},
date = {2002-11-01},
journal = {Curr. Biol.},
volume = {12},
number = {22},
pages = {1923--1927},
abstract = {Drosophila larval hemocytes originate from a hematopoietic organ called lymph glands, which are composed of paired lobes located along the dorsal vessel. Two mature blood cell populations are found in the circulating hemolymph: the macrophage-like plasmatocytes, and the crystal cells that contain enzymes of the immune-related melanization process. A third class of cells, called lamellocytes, are normally absent in larvae but differentiate after infection by parasites too large to be phagocytosed. Here we present evidence that the Notch signaling pathway plays an instructive role in the differentiation of crystal cells. Loss-of-function mutations in Notch result in severely decreased crystal cell numbers, whereas overexpression of Notch provokes the differentiation of high numbers of these cells. We demonstrate that, in this process, Serrate, not Delta, is the Notch ligand. In addition, Notch function is necessary for lamellocyte proliferation upon parasitization, although Notch overexpression does not result in lamellocyte production. Finally, Notch does not appear to play a role in the differentiation of the plasmatocyte lineage. This study underlines the existence of parallels in the genetic control of hematopoiesis in Drosophila and in mammals.},
keywords = {Animals, Cell Differentiation, Hematopoiesis, hoffmann, Larva, Lymphoid Tissue, M3i, Membrane Proteins, Notch, Receptors, Signal Transduction},
pubstate = {published},
tppubtype = {article}
}
Drosophila larval hemocytes originate from a hematopoietic organ called lymph glands, which are composed of paired lobes located along the dorsal vessel. Two mature blood cell populations are found in the circulating hemolymph: the macrophage-like plasmatocytes, and the crystal cells that contain enzymes of the immune-related melanization process. A third class of cells, called lamellocytes, are normally absent in larvae but differentiate after infection by parasites too large to be phagocytosed. Here we present evidence that the Notch signaling pathway plays an instructive role in the differentiation of crystal cells. Loss-of-function mutations in Notch result in severely decreased crystal cell numbers, whereas overexpression of Notch provokes the differentiation of high numbers of these cells. We demonstrate that, in this process, Serrate, not Delta, is the Notch ligand. In addition, Notch function is necessary for lamellocyte proliferation upon parasitization, although Notch overexpression does not result in lamellocyte production. Finally, Notch does not appear to play a role in the differentiation of the plasmatocyte lineage. This study underlines the existence of parallels in the genetic control of hematopoiesis in Drosophila and in mammals.
Ligoxygakis Petros, Pelte Nadège, Hoffmann Jules A, Reichhart Jean-Marc
Activation of Drosophila Toll during fungal infection by a blood serine protease Article de journal
Dans: Science, vol. 297, no. 5578, p. 114–116, 2002, ISSN: 1095-9203.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Surface, Chromosome Mapping, Escherichia coli, Female, Gene Expression Regulation, Genes, Gram-Positive Cocci, Hemolymph, hoffmann, Hypocreales, Insect, Insect Proteins, M3i, Male, Mutation, Protein Sorting Signals, Protein Structure, Receptors, reichhart, Serine Endopeptidases, Tertiary, Toll-Like Receptors
@article{ligoxygakis_activation_2002,
title = {Activation of Drosophila Toll during fungal infection by a blood serine protease},
author = {Petros Ligoxygakis and Nadège Pelte and Jules A Hoffmann and Jean-Marc Reichhart},
doi = {10.1126/science.1072391},
issn = {1095-9203},
year = {2002},
date = {2002-07-01},
journal = {Science},
volume = {297},
number = {5578},
pages = {114--116},
abstract = {Drosophila host defense to fungal and Gram-positive bacterial infection is mediated by the Spaetzle/Toll/cactus gene cassette. It has been proposed that Toll does not function as a pattern recognition receptor per se but is activated through a cleaved form of the cytokine Spaetzle. The upstream events linking infection to the cleavage of Spaetzle have long remained elusive. Here we report the identification of a central component of the fungal activation of Toll. We show that ethylmethane sulfonate-induced mutations in the persephone gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection.},
keywords = {Animals, Cell Surface, Chromosome Mapping, Escherichia coli, Female, Gene Expression Regulation, Genes, Gram-Positive Cocci, Hemolymph, hoffmann, Hypocreales, Insect, Insect Proteins, M3i, Male, Mutation, Protein Sorting Signals, Protein Structure, Receptors, reichhart, Serine Endopeptidases, Tertiary, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Drosophila host defense to fungal and Gram-positive bacterial infection is mediated by the Spaetzle/Toll/cactus gene cassette. It has been proposed that Toll does not function as a pattern recognition receptor per se but is activated through a cleaved form of the cytokine Spaetzle. The upstream events linking infection to the cleavage of Spaetzle have long remained elusive. Here we report the identification of a central component of the fungal activation of Toll. We show that ethylmethane sulfonate-induced mutations in the persephone gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection.
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.
Tauszig-Delamasure Servane, Bilak Hana, Capovilla Maria, Hoffmann Jules A, Imler Jean-Luc
Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections Article de journal
Dans: Nature Immunology, vol. 3, no. 1, p. 91–97, 2002, ISSN: 1529-2908.
Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Amino Acid, Animals, Antigens, Antimicrobial Cationic Peptides, Cell Surface, Chromosome Mapping, Differentiation, Disease Susceptibility, Enterococcus faecalis, Epistasis, Escherichia coli, Female, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Gram-Negative Bacteria, hoffmann, Hypocreales, imler, Immunologic, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Myeloid Differentiation Factor 88, Protein Structure, Protein-Serine-Threonine Kinases, Receptors, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Signal Transducing, Tertiary, Toll-Like Receptors, Transfection
@article{tauszig-delamasure_drosophila_2002,
title = {Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections},
author = {Servane Tauszig-Delamasure and Hana Bilak and Maria Capovilla and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1038/ni747},
issn = {1529-2908},
year = {2002},
date = {2002-01-01},
journal = {Nature Immunology},
volume = {3},
number = {1},
pages = {91--97},
abstract = {We report here the identification and functional characterization of DmMyD88, a gene encoding the Drosophila homolog of mammalian MyD88. DmMyD88 combines a Toll-IL-1R homology (TIR) domain and a death domain. Overexpression of DmMyD88 was sufficient to induce expression of the antifungal peptide Drosomycin, and induction of Drosomycin was markedly reduced in DmMyD88-mutant flies. DmMyD88 interacted with Toll through its TIR domain and required the death domain proteins Tube and Pelle to activate expression of Drs, which encodes Drosomycin. DmMyD88-mutant flies were highly susceptible to infection by fungi and Gram-positive bacteria, but resisted Gram-negative bacterial infection much as did wild-type flies. Phenotypic comparison of DmMyD88-mutant flies and MyD88-deficient mice showed essential differences in the control of Gram-negative infection in insects and mammals.},
keywords = {Adaptor Proteins, Amino Acid, Animals, Antigens, Antimicrobial Cationic Peptides, Cell Surface, Chromosome Mapping, Differentiation, Disease Susceptibility, Enterococcus faecalis, Epistasis, Escherichia coli, Female, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Gram-Negative Bacteria, hoffmann, Hypocreales, imler, Immunologic, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Myeloid Differentiation Factor 88, Protein Structure, Protein-Serine-Threonine Kinases, Receptors, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Signal Transducing, Tertiary, Toll-Like Receptors, Transfection},
pubstate = {published},
tppubtype = {article}
}
We report here the identification and functional characterization of DmMyD88, a gene encoding the Drosophila homolog of mammalian MyD88. DmMyD88 combines a Toll-IL-1R homology (TIR) domain and a death domain. Overexpression of DmMyD88 was sufficient to induce expression of the antifungal peptide Drosomycin, and induction of Drosomycin was markedly reduced in DmMyD88-mutant flies. DmMyD88 interacted with Toll through its TIR domain and required the death domain proteins Tube and Pelle to activate expression of Drs, which encodes Drosomycin. DmMyD88-mutant flies were highly susceptible to infection by fungi and Gram-positive bacteria, but resisted Gram-negative bacterial infection much as did wild-type flies. Phenotypic comparison of DmMyD88-mutant flies and MyD88-deficient mice showed essential differences in the control of Gram-negative infection in insects and mammals.
Imler Jean-Luc, Hoffmann Jules A
Toll receptors in Drosophila: a family of molecules regulating development and immunity Article de journal
Dans: Current Topics in Microbiology and Immunology, vol. 270, p. 63–79, 2002, ISSN: 0070-217X.
Résumé | BibTeX | Étiquettes: Animals, Cell Surface, Genetic, Gram-Negative Bacteria, hoffmann, imler, M3i, Receptors, Signal Transduction, Toll-Like Receptors, Transcription
@article{imler_toll_2002,
title = {Toll receptors in Drosophila: a family of molecules regulating development and immunity},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {0070-217X},
year = {2002},
date = {2002-01-01},
journal = {Current Topics in Microbiology and Immunology},
volume = {270},
pages = {63--79},
abstract = {In recent years, Toll-like receptors (TLRs) have emerged as key receptors which detect microbes and initiate an inflammatory response. The Toll receptor was originally identified and characterized 14 years ago for its role in the embryonic development of the fruit-fly Drosophila melanogaster. Subsequently, it was also shown to be an essential component of the signaling pathway mediating the anti-fungal host defense in this model organism. New factors involved in the activation of the Toll receptor or in intracytoplasmic signaling during the immune response in Drosophila have recently been identified. The existence of significant functional differences between mammalian TLRs and Drosophila Toll receptors is also becoming apparent.},
keywords = {Animals, Cell Surface, Genetic, Gram-Negative Bacteria, hoffmann, imler, M3i, Receptors, Signal Transduction, Toll-Like Receptors, Transcription},
pubstate = {published},
tppubtype = {article}
}
In recent years, Toll-like receptors (TLRs) have emerged as key receptors which detect microbes and initiate an inflammatory response. The Toll receptor was originally identified and characterized 14 years ago for its role in the embryonic development of the fruit-fly Drosophila melanogaster. Subsequently, it was also shown to be an essential component of the signaling pathway mediating the anti-fungal host defense in this model organism. New factors involved in the activation of the Toll receptor or in intracytoplasmic signaling during the immune response in Drosophila have recently been identified. The existence of significant functional differences between mammalian TLRs and Drosophila Toll receptors is also becoming apparent.
2001
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.
Mueller C G, Cremer I, Paulet P E, Niida S, Maeda N, Lebeque S, Fridman W H, Sautès-Fridman C
Mannose receptor ligand-positive cells express the metalloprotease decysin in the B cell follicle Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 167, no. 9, p. 5052–5060, 2001, ISSN: 0022-1767.
Résumé | Liens | BibTeX | Étiquettes: ADAM Proteins, Amino Acid Sequence, Animals, B-Lymphocytes, C-Type, Cell Surface, Cloning, Dendritic Cells, Follicular, Germinal Center, Humans, Inbred BALB C, Lectins, ligands, Macrophage Colony-Stimulating Factor, Macrophages, Mannose-Binding Lectins, Metalloendopeptidases, Mice, Molecular, Molecular Sequence Data, Receptors, SPLEEN, Team-Mueller
@article{mueller_mannose_2001,
title = {Mannose receptor ligand-positive cells express the metalloprotease decysin in the B cell follicle},
author = {C G Mueller and I Cremer and P E Paulet and S Niida and N Maeda and S Lebeque and W H Fridman and C Sautès-Fridman},
doi = {10.4049/jimmunol.167.9.5052},
issn = {0022-1767},
year = {2001},
date = {2001-11-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {167},
number = {9},
pages = {5052--5060},
abstract = {Decysin, a gene encoding a disintegrin metalloprotease, is transcribed in human dendritic cells (DC) and germinal centers (GC). We have cloned its murine homologue and show that it is processed by the endoprotease furin before secretion of the catalytic domain. We have defined the cell types that express decysin in mouse spleen in the course of an immune response to T cell-dependent Ags. Like in humans, decysin is transcribed by activated CD11c(+) DC that enter the T cell zone from the marginal zone (MZ). In the GC, decysin is expressed by follicular DC and tingible body macrophages. In addition, a MZ cell population expresses decysin and appears to migrate into the B cell follicle. The majority of these follicle-homing cells express the mannose receptor ligand, a marker for the macrophage-like MZ metallophils. The follicle-homing cells are M-CSF dependent, as they are absent in op/op mice that lack functional M-CSF. This suggests that mannose receptor ligand(+) MZ metallophils differentiate into cells that migrate from the MZ into the B cell follicle. Decysin represents the first marker for this previously unrecognized cell population of the mouse spleen, which may represent a precursor for GCDC and may be specialized in the transport of unprocessed Ag from the MZ into developing GC.},
keywords = {ADAM Proteins, Amino Acid Sequence, Animals, B-Lymphocytes, C-Type, Cell Surface, Cloning, Dendritic Cells, Follicular, Germinal Center, Humans, Inbred BALB C, Lectins, ligands, Macrophage Colony-Stimulating Factor, Macrophages, Mannose-Binding Lectins, Metalloendopeptidases, Mice, Molecular, Molecular Sequence Data, Receptors, SPLEEN, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Decysin, a gene encoding a disintegrin metalloprotease, is transcribed in human dendritic cells (DC) and germinal centers (GC). We have cloned its murine homologue and show that it is processed by the endoprotease furin before secretion of the catalytic domain. We have defined the cell types that express decysin in mouse spleen in the course of an immune response to T cell-dependent Ags. Like in humans, decysin is transcribed by activated CD11c(+) DC that enter the T cell zone from the marginal zone (MZ). In the GC, decysin is expressed by follicular DC and tingible body macrophages. In addition, a MZ cell population expresses decysin and appears to migrate into the B cell follicle. The majority of these follicle-homing cells express the mannose receptor ligand, a marker for the macrophage-like MZ metallophils. The follicle-homing cells are M-CSF dependent, as they are absent in op/op mice that lack functional M-CSF. This suggests that mannose receptor ligand(+) MZ metallophils differentiate into cells that migrate from the MZ into the B cell follicle. Decysin represents the first marker for this previously unrecognized cell population of the mouse spleen, which may represent a precursor for GCDC and may be specialized in the transport of unprocessed Ag from the MZ into developing GC.
Postawski K., Olech-Fudali E., Korobowicz E., Jakowicki J. A., Keith G., Baranowski W.
[Hydrophobic DNA adducts in relationship to estrogen and progesterone receptors content in human uterine cancer.] Article de journal
Dans: Ginekol Pol, vol. 72, no. 9, p. 709-16, 2001, (0017-0011 Journal Article).
Résumé | BibTeX | Étiquettes: Abstract, Adducts/*analysis, Autoradiography, DNA, English, Estrogen/*analysis, Female, Human, Neoplasm/*analysis, Neoplasms/genetics/*pathology, Progesterone/*analysis, Receptors, Uterine
@article{,
title = {[Hydrophobic DNA adducts in relationship to estrogen and progesterone receptors content in human uterine cancer.]},
author = { K. Postawski and E. Olech-Fudali and E. Korobowicz and J. A. Jakowicki and G. Keith and W. Baranowski},
year = {2001},
date = {2001-01-01},
journal = {Ginekol Pol},
volume = {72},
number = {9},
pages = {709-16},
abstract = {OBJECTIVE: Determination of the relationship between hydrophobic DNA adducts (A) and estrogen receptors (ER) and progesterone (PR) receptor status in uterine cancers. METHODS: Using the P1 enriched version of 32P-postlabeling for hydrophobic DNA adducts detection on polyethyleneimine (PEI) cellulose thin layer chromatograms (TLC) we examined 11 uterine cancer DNAs. The quantification of the adducts was performed by Cerenkov counting of the spots. ER and PR status was recognized histochemically and H-score estimate was performed for each investigated cancer tissue. Patterns of uterine cancer DNA adducts were compared to the maps of adducts recognized in normal human endometrium. RESULTS: In three of the studied uterine cancers there was no positive staining of ER and PR; in one case there was a weak ER staining but PR staining was negative. In ER negative tumors the A level was significantly higher than in ER positive cancers (138.1 +/- 64.1 vs. 49.7 +/- 26.8 adducts per 10(9) nucleotides, respectively, p < 0.05). Highest A levels were found in two ER and PR negative G3 metastatic tumors. Finally, in all investigated cancers there was a strong, inverse correlation between ER content and A level (r = -0.67, p < 0.03). In addition, the correlation between PR level and A was of borderline significance (r = -0.6},
note = {0017-0011
Journal Article},
keywords = {Abstract, Adducts/*analysis, Autoradiography, DNA, English, Estrogen/*analysis, Female, Human, Neoplasm/*analysis, Neoplasms/genetics/*pathology, Progesterone/*analysis, Receptors, Uterine},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: Determination of the relationship between hydrophobic DNA adducts (A) and estrogen receptors (ER) and progesterone (PR) receptor status in uterine cancers. METHODS: Using the P1 enriched version of 32P-postlabeling for hydrophobic DNA adducts detection on polyethyleneimine (PEI) cellulose thin layer chromatograms (TLC) we examined 11 uterine cancer DNAs. The quantification of the adducts was performed by Cerenkov counting of the spots. ER and PR status was recognized histochemically and H-score estimate was performed for each investigated cancer tissue. Patterns of uterine cancer DNA adducts were compared to the maps of adducts recognized in normal human endometrium. RESULTS: In three of the studied uterine cancers there was no positive staining of ER and PR; in one case there was a weak ER staining but PR staining was negative. In ER negative tumors the A level was significantly higher than in ER positive cancers (138.1 +/- 64.1 vs. 49.7 +/- 26.8 adducts per 10(9) nucleotides, respectively, p < 0.05). Highest A levels were found in two ER and PR negative G3 metastatic tumors. Finally, in all investigated cancers there was a strong, inverse correlation between ER content and A level (r = -0.67, p < 0.03). In addition, the correlation between PR level and A was of borderline significance (r = -0.6
Imler Jean-Luc, Hoffmann Jules A
Toll receptors in innate immunity Article de journal
Dans: Trends in Cell Biology, vol. 11, no. 7, p. 304–311, 2001, ISSN: 0962-8924.
Résumé | BibTeX | Étiquettes: Animals, Cell Surface, hoffmann, Humans, imler, Immunity, Immunologic, Innate, M3i, Membrane Glycoproteins, Membrane Proteins, Receptors, Toll-Like Receptors
@article{imler_toll_2001,
title = {Toll receptors in innate immunity},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {0962-8924},
year = {2001},
date = {2001-01-01},
journal = {Trends in Cell Biology},
volume = {11},
number = {7},
pages = {304--311},
abstract = {Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to infectious agents. In addition, the cells and molecules operating during this early stage of the immune response in vertebrates have a decisive impact on the shaping of the subsequent adaptive response. Genetic studies initially performed in the fruitfly Drosophila and later in mice have revealed the importance of proteins of the Toll family in the innate immune response. We present here our current understanding of the role of this evolutionary ancient family of proteins that are thought to function as cytokine receptors (Toll in Drosophila) or pattern-recognition receptors (TLRs in mammals) and activate similar, albeit non-identical, signal-transduction pathways in flies and mammals.},
keywords = {Animals, Cell Surface, hoffmann, Humans, imler, Immunity, Immunologic, Innate, M3i, Membrane Glycoproteins, Membrane Proteins, Receptors, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to infectious agents. In addition, the cells and molecules operating during this early stage of the immune response in vertebrates have a decisive impact on the shaping of the subsequent adaptive response. Genetic studies initially performed in the fruitfly Drosophila and later in mice have revealed the importance of proteins of the Toll family in the innate immune response. We present here our current understanding of the role of this evolutionary ancient family of proteins that are thought to function as cytokine receptors (Toll in Drosophila) or pattern-recognition receptors (TLRs in mammals) and activate similar, albeit non-identical, signal-transduction pathways in flies and mammals.
2000
Casimir J R, Iterbeke K, Nest W Van Den, Trescol-Biémont M C, Dumortier H, Muller S, Gerlier D, Rabourdin-Combe C, Tourwé D, Paris J
Conformational restriction of the Tyr53 side-chain in the decapeptide HE Article de journal
Dans: The Journal of Peptide Research: Official Journal of the American Peptide Society, vol. 56, no. 6, p. 398–408, 2000, ISSN: 1397-002X.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Antigen, Antigen-Presenting Cells, B-Lymphocytes, Chemical, Chickens, Dumortier, I2CT, Major Histocompatibility Complex, Mice, Models, Molecular Sequence Data, Muramidase, Peptide Biosynthesis, Peptides, Phenylalanine, Protein Binding, Protein Conformation, Receptors, T-Cell, Team-Dumortier, Temperature, Tyrosine
@article{casimir_conformational_2000,
title = {Conformational restriction of the Tyr53 side-chain in the decapeptide HE},
author = {J R Casimir and K Iterbeke and W Van Den Nest and M C Trescol-Biémont and H Dumortier and S Muller and D Gerlier and C Rabourdin-Combe and D Tourwé and J Paris},
doi = {10.1034/j.1399-3011.2000.00777.x},
issn = {1397-002X},
year = {2000},
date = {2000-12-01},
journal = {The Journal of Peptide Research: Official Journal of the American Peptide Society},
volume = {56},
number = {6},
pages = {398--408},
abstract = {A series of conformationally restricted analogs of the hen egg lysozyme (HEL) decapeptide 52-61 in which the conformationally flexible Tyr53 residue was replaced by several more constrained tyrosine and phenylalanine analogs was prepared. Among these tyrosine and phenylalanine analogs were 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (Htc), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), 4-amino- 1,2,4,5-tetrahydro-8-hydroxy-2-benzazepine-3-one (Hba), 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one (Aba), 2-amino-6-hydroxytetralin-2-carboxylic acid (Hat) and 2-amino-5-hydroxyindan-2-carboxylic acid (Hai) in which the rotations around Calpha-Cbeta and Cbeta-Cgamma were restricted because of cyclization of the side-chain to the backbone. Synthesis of Pht-Hba-Gly-OH using a modification of the Flynn and de Laszlo procedure is described. Analogs of beta-methyltyrosine (beta-MeTyr) in which the side-chains were biased to particular side-chain torsional angles because of substitution at the beta-hydrogens were also prepared. These analogs of HEL[52-61] peptide were tested for their ability to bind to the major histocompatibility complex class II I-Ak molecule and to be recognized in this context by two T-cell hybridomas, specific for the parent peptide HEL[52-61]. The data showed that the conformation and also the configuration of the Tyr53 residue influenced both the binding of the peptide to I-Ak and the recognition of the peptide/I-Ak complex by a T-cell receptor.},
keywords = {Amino Acid Sequence, Animals, Antigen, Antigen-Presenting Cells, B-Lymphocytes, Chemical, Chickens, Dumortier, I2CT, Major Histocompatibility Complex, Mice, Models, Molecular Sequence Data, Muramidase, Peptide Biosynthesis, Peptides, Phenylalanine, Protein Binding, Protein Conformation, Receptors, T-Cell, Team-Dumortier, Temperature, Tyrosine},
pubstate = {published},
tppubtype = {article}
}
A series of conformationally restricted analogs of the hen egg lysozyme (HEL) decapeptide 52-61 in which the conformationally flexible Tyr53 residue was replaced by several more constrained tyrosine and phenylalanine analogs was prepared. Among these tyrosine and phenylalanine analogs were 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (Htc), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), 4-amino- 1,2,4,5-tetrahydro-8-hydroxy-2-benzazepine-3-one (Hba), 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one (Aba), 2-amino-6-hydroxytetralin-2-carboxylic acid (Hat) and 2-amino-5-hydroxyindan-2-carboxylic acid (Hai) in which the rotations around Calpha-Cbeta and Cbeta-Cgamma were restricted because of cyclization of the side-chain to the backbone. Synthesis of Pht-Hba-Gly-OH using a modification of the Flynn and de Laszlo procedure is described. Analogs of beta-methyltyrosine (beta-MeTyr) in which the side-chains were biased to particular side-chain torsional angles because of substitution at the beta-hydrogens were also prepared. These analogs of HEL[52-61] peptide were tested for their ability to bind to the major histocompatibility complex class II I-Ak molecule and to be recognized in this context by two T-cell hybridomas, specific for the parent peptide HEL[52-61]. The data showed that the conformation and also the configuration of the Tyr53 residue influenced both the binding of the peptide to I-Ak and the recognition of the peptide/I-Ak complex by a T-cell receptor.
Lagueux Marie, Perrodou E, Levashina Elena A, Capovilla Maria, Hoffmann Jules A
Constitutive expression of a complement-like protein in toll and JAK gain-of-function mutants of Drosophila Article de journal
Dans: Proc. Natl. Acad. Sci. U.S.A., vol. 97, no. 21, p. 11427–11432, 2000, ISSN: 0027-8424.
Résumé | Liens | BibTeX | Étiquettes: alpha-Macroglobulins, Amino Acid, Animals, Cell Surface, Complement C3, Esters, Genetic, hoffmann, Insect Proteins, Janus Kinases, M3i, Membrane Glycoproteins, Mutation, Protein-Tyrosine Kinases, Proteins, Receptors, Sequence Homology, Sulfhydryl Compounds, Toll-Like Receptors, Transcription, Transcription Factors
@article{lagueux_constitutive_2000,
title = {Constitutive expression of a complement-like protein in toll and JAK gain-of-function mutants of Drosophila},
author = {Marie Lagueux and E Perrodou and Elena A Levashina and Maria Capovilla and Jules A Hoffmann},
doi = {10.1073/pnas.97.21.11427},
issn = {0027-8424},
year = {2000},
date = {2000-10-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {97},
number = {21},
pages = {11427--11432},
abstract = {We show that Drosophila expresses four genes encoding proteins with significant similarities with the thiolester-containing proteins of the complement C3/alpha(2)-macroglobulin superfamily. The genes are transcribed at a low level during all stages of development, and their expression is markedly up-regulated after an immune challenge. For one of these genes, which is predominantly expressed in the larval fat body, we observe a constitutive expression in gain-of-function mutants of the Janus kinase (JAK) hop and a reduced inducibility in loss-of-function hop mutants. We also observe a constitutive expression in gain-of-function Toll mutants. We discuss the possible roles of these novel complement-like proteins in the Drosophila host defense.},
keywords = {alpha-Macroglobulins, Amino Acid, Animals, Cell Surface, Complement C3, Esters, Genetic, hoffmann, Insect Proteins, Janus Kinases, M3i, Membrane Glycoproteins, Mutation, Protein-Tyrosine Kinases, Proteins, Receptors, Sequence Homology, Sulfhydryl Compounds, Toll-Like Receptors, Transcription, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
We show that Drosophila expresses four genes encoding proteins with significant similarities with the thiolester-containing proteins of the complement C3/alpha(2)-macroglobulin superfamily. The genes are transcribed at a low level during all stages of development, and their expression is markedly up-regulated after an immune challenge. For one of these genes, which is predominantly expressed in the larval fat body, we observe a constitutive expression in gain-of-function mutants of the Janus kinase (JAK) hop and a reduced inducibility in loss-of-function hop mutants. We also observe a constitutive expression in gain-of-function Toll mutants. We discuss the possible roles of these novel complement-like proteins in the Drosophila host defense.
Rutschmann Sophie, Jung Alain C, Zhou R, Silverman N, Hoffmann Jules A, Ferrandon Dominique
Role of Drosophila IKK gamma in a toll-independent antibacterial immune response Article de journal
Dans: Nat. Immunol., vol. 1, no. 4, p. 342–347, 2000, ISSN: 1529-2908.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antigens, Bacterial, Cell Surface, ferrandon, Gene Expression Regulation, hoffmann, I-kappa B Kinase, Immunity, Innate, Insect Proteins, M3i, Membrane Glycoproteins, Protein-Serine-Threonine Kinases, Receptors, Signal Transduction, Toll-Like Receptors, Transcription Factors
@article{rutschmann_role_2000,
title = {Role of Drosophila IKK gamma in a toll-independent antibacterial immune response},
author = {Sophie Rutschmann and Alain C Jung and R Zhou and N Silverman and Jules A Hoffmann and Dominique Ferrandon},
doi = {10.1038/79801},
issn = {1529-2908},
year = {2000},
date = {2000-10-01},
journal = {Nat. Immunol.},
volume = {1},
number = {4},
pages = {342--347},
abstract = {We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila.},
keywords = {Animals, Antigens, Bacterial, Cell Surface, ferrandon, Gene Expression Regulation, hoffmann, I-kappa B Kinase, Immunity, Innate, Insect Proteins, M3i, Membrane Glycoproteins, Protein-Serine-Threonine Kinases, Receptors, Signal Transduction, Toll-Like Receptors, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila.
Tauszig Servane, Jouanguy Emmanuelle, Hoffmann Jules A, Imler Jean-Luc
Toll-related receptors and the control of antimicrobial peptide expression in Drosophila Article de journal
Dans: Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 19, p. 10520–10525, 2000, ISSN: 0027-8424.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Animals, Anti-Bacterial Agents, Blotting, Cell Line, Cell Surface, hoffmann, imler, M3i, Membrane Glycoproteins, Multigene Family, Northern, Peptides, Receptors, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptors
@article{tauszig_toll-related_2000,
title = {Toll-related receptors and the control of antimicrobial peptide expression in Drosophila},
author = {Servane Tauszig and Emmanuelle Jouanguy and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1073/pnas.180130797},
issn = {0027-8424},
year = {2000},
date = {2000-09-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {97},
number = {19},
pages = {10520--10525},
abstract = {Insects defend themselves against infectious microorganisms by synthesizing potent antimicrobial peptides. Drosophila has appeared in recent years as a favorable model to study this innate host defense. A genetic analysis of the regulation of the antifungal peptide drosomycin has demonstrated a key role for the transmembrane receptor Toll, which prompted the search for mammalian homologs. Two of these, Toll-like receptor (TLR)2 and TLR4, recently were shown to play a critical role in innate immunity against bacteria. Here we describe six additional Toll-related genes (Toll-3 to Toll-8) in Drosophila in addition to 18-wheeler. Two of these genes, Toll-3 and Toll-4, are expressed at a low level. Toll-6, -7, and -8, on the other hand, are expressed at high levels during embryogenesis and molting, suggesting that, like Toll and 18w, they perform developmental functions. Finally, Toll-5 is expressed only in larvae and adults. By using chimeric constructs, we have tested the capacity of the signaling Toll/IL-1R homology domains of these receptors to activate antimicrobial peptide promoters and found that only Toll and Toll-5 can activate the drosomycin promoter in transfected cells, thus demonstrating specificity at the level of the Toll/IL-1R homology domain. In contrast, none of these constructs activated antibacterial peptide promoters, suggesting that Toll-related receptors are not involved in the regulation of antibacterial peptide expression. This result was independently confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide.},
keywords = {Amino Acid, Animals, Anti-Bacterial Agents, Blotting, Cell Line, Cell Surface, hoffmann, imler, M3i, Membrane Glycoproteins, Multigene Family, Northern, Peptides, Receptors, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Insects defend themselves against infectious microorganisms by synthesizing potent antimicrobial peptides. Drosophila has appeared in recent years as a favorable model to study this innate host defense. A genetic analysis of the regulation of the antifungal peptide drosomycin has demonstrated a key role for the transmembrane receptor Toll, which prompted the search for mammalian homologs. Two of these, Toll-like receptor (TLR)2 and TLR4, recently were shown to play a critical role in innate immunity against bacteria. Here we describe six additional Toll-related genes (Toll-3 to Toll-8) in Drosophila in addition to 18-wheeler. Two of these genes, Toll-3 and Toll-4, are expressed at a low level. Toll-6, -7, and -8, on the other hand, are expressed at high levels during embryogenesis and molting, suggesting that, like Toll and 18w, they perform developmental functions. Finally, Toll-5 is expressed only in larvae and adults. By using chimeric constructs, we have tested the capacity of the signaling Toll/IL-1R homology domains of these receptors to activate antimicrobial peptide promoters and found that only Toll and Toll-5 can activate the drosomycin promoter in transfected cells, thus demonstrating specificity at the level of the Toll/IL-1R homology domain. In contrast, none of these constructs activated antibacterial peptide promoters, suggesting that Toll-related receptors are not involved in the regulation of antibacterial peptide expression. This result was independently confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide.
Imler Jean-Luc, Hoffmann Jules A
Signaling mechanisms in the antimicrobial host defense of Drosophila Article de journal
Dans: Current Opinion in Microbiology, vol. 3, no. 1, p. 16–22, 2000, ISSN: 1369-5274.
Résumé | BibTeX | Étiquettes: Animals, Anti-Infective Agents, Cell Surface, Gene Expression Regulation, Genes, hoffmann, imler, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, Signal Transduction, Toll-Like Receptors
@article{imler_signaling_2000,
title = {Signaling mechanisms in the antimicrobial host defense of Drosophila},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {1369-5274},
year = {2000},
date = {2000-02-01},
journal = {Current Opinion in Microbiology},
volume = {3},
number = {1},
pages = {16--22},
abstract = {Drosophila has appeared in recent years as a powerful model to study innate immunity. Several papers published in the past year shed light on the role of the three Rel proteins Dorsal, Dif and Relish in the regulation of antimicrobial peptide expression. In addition, the discovery that a blood serine protease inhibitor is involved in the control of the antifungal response indicates that Toll is activated upon triggering of a proteolytic cascade and does not function as a Drosophila pattern recognition receptor.},
keywords = {Animals, Anti-Infective Agents, Cell Surface, Gene Expression Regulation, Genes, hoffmann, imler, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Drosophila has appeared in recent years as a powerful model to study innate immunity. Several papers published in the past year shed light on the role of the three Rel proteins Dorsal, Dif and Relish in the regulation of antimicrobial peptide expression. In addition, the discovery that a blood serine protease inhibitor is involved in the control of the antifungal response indicates that Toll is activated upon triggering of a proteolytic cascade and does not function as a Drosophila pattern recognition receptor.
Postawski K., Olech-Fudali E., Jakowicki J. A., Korobowicz E., Keith G., Baranowski W.
[Overall genomic DNA methylation in relation to estrogen] Article de journal
Dans: Ginekol Pol, vol. 71, no. 9, p. 1206-11, 2000, (0017-0011 Journal Article).
Résumé | BibTeX | Étiquettes: 80, Abstract, Aged, and, Biopsy, DNA, English, Estrogen/*metabolism, Female, Gov't, Human, Methylases/metabolism, Methylation, Middle, modification, Neoplasms/*metabolism/*pathology, Non-U.S., over, Progesterone/*metabolism, Receptors, Support, Uterine, Uterus/*metabolism/pathology
@article{,
title = {[Overall genomic DNA methylation in relation to estrogen]},
author = { K. Postawski and E. Olech-Fudali and J. A. Jakowicki and E. Korobowicz and G. Keith and W. Baranowski},
year = {2000},
date = {2000-01-01},
journal = {Ginekol Pol},
volume = {71},
number = {9},
pages = {1206-11},
abstract = {Overall genomic DNA methylation was analyzed using enzymatic digestion into nucleotides, 32P postlabeling, two-dimensional thin-layer chromatography on cellulose plates and phosphobioimaging quantitation, in relation to immunohistochemically measured estrogen (ER) and progesterone receptor (PR) status of 15 uterine cancers. Mean 5-methyldeoxycytosine (m5dC) content did not differ between ER-positive and ER-negative neoplasms. Highest values of m5dC were noted both in ER-negative and ER-positive tumors. Additionally, there was no low DNA methylation in ER negative uterine cancer tissues. Decrease of the overall genomic DNA methylation could be related to the increase of ER/PR ratio, however it was not significant in our investigation. The potential role of steroid receptors status in uterine cancer tissue is discussed.},
note = {0017-0011
Journal Article},
keywords = {80, Abstract, Aged, and, Biopsy, DNA, English, Estrogen/*metabolism, Female, Gov't, Human, Methylases/metabolism, Methylation, Middle, modification, Neoplasms/*metabolism/*pathology, Non-U.S., over, Progesterone/*metabolism, Receptors, Support, Uterine, Uterus/*metabolism/pathology},
pubstate = {published},
tppubtype = {article}
}
Overall genomic DNA methylation was analyzed using enzymatic digestion into nucleotides, 32P postlabeling, two-dimensional thin-layer chromatography on cellulose plates and phosphobioimaging quantitation, in relation to immunohistochemically measured estrogen (ER) and progesterone receptor (PR) status of 15 uterine cancers. Mean 5-methyldeoxycytosine (m5dC) content did not differ between ER-positive and ER-negative neoplasms. Highest values of m5dC were noted both in ER-negative and ER-positive tumors. Additionally, there was no low DNA methylation in ER negative uterine cancer tissues. Decrease of the overall genomic DNA methylation could be related to the increase of ER/PR ratio, however it was not significant in our investigation. The potential role of steroid receptors status in uterine cancer tissue is discussed.
Imler Jean-Luc, Tauszig Servane, Jouanguy Emmanuelle, Forestier C, Hoffmann Jules A
LPS-induced immune response in Drosophila Article de journal
Dans: Journal of Endotoxin Research, vol. 6, no. 6, p. 459–462, 2000, ISSN: 0968-0519.
Résumé | BibTeX | Étiquettes: Animals, Biological, Cell Line, Cell Surface, Defensins, Genes, Genetic, hoffmann, imler, Insect, Insect Proteins, Lipopolysaccharides, M3i, Membrane Glycoproteins, Models, Mutation, Promoter Regions, Receptors, Signal Transduction, Toll-Like Receptors
@article{imler_lps-induced_2000,
title = {LPS-induced immune response in Drosophila},
author = {Jean-Luc Imler and Servane Tauszig and Emmanuelle Jouanguy and C Forestier and Jules A Hoffmann},
issn = {0968-0519},
year = {2000},
date = {2000-01-01},
journal = {Journal of Endotoxin Research},
volume = {6},
number = {6},
pages = {459--462},
abstract = {The study of the regulation of the inducible synthesis of antimicrobial peptides in Drosophila melanogaster has established this insect as a powerful model in which to study innate immunity. In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity. We report here that injection of LPS into flies induces an immune response, suggesting that LPS receptors are used in Drosophila to detect Gram-negative bacteria infection. We have identified in the recently sequenced genome of Drosophila eight genes coding for Toll-like receptors in addition to Toll, which may function as LPS receptors. However, overexpression of a selection of these genes in tissue-culture cells does not result in up-regulation of the antibacterial peptide genes. These results are discussed in light of the recent data from genetic screens aimed at identifying the genes controlling the antibacterial response in Drosophila.},
keywords = {Animals, Biological, Cell Line, Cell Surface, Defensins, Genes, Genetic, hoffmann, imler, Insect, Insect Proteins, Lipopolysaccharides, M3i, Membrane Glycoproteins, Models, Mutation, Promoter Regions, Receptors, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
The study of the regulation of the inducible synthesis of antimicrobial peptides in Drosophila melanogaster has established this insect as a powerful model in which to study innate immunity. In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity. We report here that injection of LPS into flies induces an immune response, suggesting that LPS receptors are used in Drosophila to detect Gram-negative bacteria infection. We have identified in the recently sequenced genome of Drosophila eight genes coding for Toll-like receptors in addition to Toll, which may function as LPS receptors. However, overexpression of a selection of these genes in tissue-culture cells does not result in up-regulation of the antibacterial peptide genes. These results are discussed in light of the recent data from genetic screens aimed at identifying the genes controlling the antibacterial response in Drosophila.
Imler Jean-Luc, Hoffmann Jules A
Toll and Toll-like proteins: an ancient family of receptors signaling infection Article de journal
Dans: Reviews in Immunogenetics, vol. 2, no. 3, p. 294–304, 2000, ISSN: 1398-1714.
Résumé | BibTeX | Étiquettes: Adaptor Proteins, Animals, Antigens, Autoantigens, CD14, Cell Adhesion Molecules, Cell Surface, Differentiation, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, I-kappa B Proteins, imler, Immunity, Immunologic, infection, Innate, Insect Proteins, Interleukin-1 Receptor-Associated Kinases, Knockout, Larva, Lipopolysaccharides, M3i, Mammals, MAP Kinase Signaling System, Membrane Glycoproteins, Membrane Proteins, Mice, Multigene Family, Myeloid Differentiation Factor 88, NF-kappa B, peptidoglycan, Phosphorylation, Post-Translational, Protein Kinases, Protein Processing, Protein Structure, Receptors, Recombinant Fusion Proteins, Signal Transducing, Signal Transduction, Teichoic Acids, Tertiary, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptor 6, Toll-Like Receptor 9, Toll-Like Receptors, Ubiquitins
@article{imler_toll_2000,
title = {Toll and Toll-like proteins: an ancient family of receptors signaling infection},
author = {Jean-Luc Imler and Jules A Hoffmann},
issn = {1398-1714},
year = {2000},
date = {2000-01-01},
journal = {Reviews in Immunogenetics},
volume = {2},
number = {3},
pages = {294--304},
abstract = {Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to microbes. It involves intracellular signaling pathways in the fruit-fly Drosophila and in mammals that show striking similarities. Recent genetic and biochemical data have revealed, in particular, that proteins of the Toll family play a critical role in the immediate response to infection. We review here the recent developments on the structural and functional characterization of this evolutionary ancient and important family of proteins, which can function as cytokine receptors (Toll in Drosophila) or pattern recognition receptors (TLR4 in mammals) and activate similar, albeit non identical signal transduction pathways, in flies and mammals.},
keywords = {Adaptor Proteins, Animals, Antigens, Autoantigens, CD14, Cell Adhesion Molecules, Cell Surface, Differentiation, DNA-Binding Proteins, Gene Expression Regulation, hoffmann, I-kappa B Proteins, imler, Immunity, Immunologic, infection, Innate, Insect Proteins, Interleukin-1 Receptor-Associated Kinases, Knockout, Larva, Lipopolysaccharides, M3i, Mammals, MAP Kinase Signaling System, Membrane Glycoproteins, Membrane Proteins, Mice, Multigene Family, Myeloid Differentiation Factor 88, NF-kappa B, peptidoglycan, Phosphorylation, Post-Translational, Protein Kinases, Protein Processing, Protein Structure, Receptors, Recombinant Fusion Proteins, Signal Transducing, Signal Transduction, Teichoic Acids, Tertiary, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptor 6, Toll-Like Receptor 9, Toll-Like Receptors, Ubiquitins},
pubstate = {published},
tppubtype = {article}
}
Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to microbes. It involves intracellular signaling pathways in the fruit-fly Drosophila and in mammals that show striking similarities. Recent genetic and biochemical data have revealed, in particular, that proteins of the Toll family play a critical role in the immediate response to infection. We review here the recent developments on the structural and functional characterization of this evolutionary ancient and important family of proteins, which can function as cytokine receptors (Toll in Drosophila) or pattern recognition receptors (TLR4 in mammals) and activate similar, albeit non identical signal transduction pathways, in flies and mammals.
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.
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.
1997
Mézière C, Viguier M, Dumortier H, Lo-Man R, Leclerc C, Guillet J G, Briand J P, Muller S
In vivo Ŧ helper cell response to retro-inverso peptidomimetics Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 159, no. 7, p. 3230–3237, 1997, ISSN: 0022-1767.
Résumé | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Antibodies, Antigen, Capsid, Capsid Proteins, Dumortier, Female, Helper-Inducer, Histocompatibility Antigens Class II, I2CT, Immunoglobulin Allotypes, Immunoglobulin G, Inbred BALB C, Injections, Intraperitoneal, Lymphocyte Activation, Mice, Molecular Sequence Data, Peptide Fragments, Poliovirus, Protein Binding, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier, Viral
@article{meziere_vivo_1997,
title = {In vivo Ŧ helper cell response to retro-inverso peptidomimetics},
author = {C Mézière and M Viguier and H Dumortier and R Lo-Man and C Leclerc and J G Guillet and J P Briand and S Muller},
issn = {0022-1767},
year = {1997},
date = {1997-10-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {159},
number = {7},
pages = {3230--3237},
abstract = {Peptide analogues containing reversed peptide bonds between each residue along the peptide sequence (retro-inverso modification) have been analyzed for their antigenic and in vivo immunogenic properties in the MHC II and Th cell response context. Two antigenic peptides were selected for this study, namely peptide 103-115 of poliovirus VP1, which is involved in the production of Abs that neutralize the infectivity of the virus, and peptide 435-446 from the third constant region of mouse heavy chain IgG2a allopeptide gamma 2ab, which mimics a corneal Ag implicated in autoimmune keratitis. In a competition assay performed in vitro using reference hybridomas of known MHC class II restriction, both retro-inverso analogues bound (although more weakly in our test) to I-Ad and/or I-Ed class II molecules. However, in both cases, this lower affinity was apparently largely compensated in vivo, as a T cell response (with IL-2 secretion), equivalent to that obtained with the wild-type peptides, was observed following immunization of BALB/c mice with the retro-inverso analogues. Moreover, these T cells proliferated and produced IL-2 in response to the cognate peptides. It is concluded that the T cell receptors of T cells primed in vivo with the retro-inverso analogues readily cross-react with parent and retro-inverso analogue-MHC complexes. The approach of using pseudopeptides containing changes involving the backbone, and not the orientation of side chains, may thus be promising to design potent immunogens for class II-restricted T cells.},
keywords = {Amino Acid Sequence, Animals, Antibodies, Antigen, Capsid, Capsid Proteins, Dumortier, Female, Helper-Inducer, Histocompatibility Antigens Class II, I2CT, Immunoglobulin Allotypes, Immunoglobulin G, Inbred BALB C, Injections, Intraperitoneal, Lymphocyte Activation, Mice, Molecular Sequence Data, Peptide Fragments, Poliovirus, Protein Binding, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier, Viral},
pubstate = {published},
tppubtype = {article}
}
Peptide analogues containing reversed peptide bonds between each residue along the peptide sequence (retro-inverso modification) have been analyzed for their antigenic and in vivo immunogenic properties in the MHC II and Th cell response context. Two antigenic peptides were selected for this study, namely peptide 103-115 of poliovirus VP1, which is involved in the production of Abs that neutralize the infectivity of the virus, and peptide 435-446 from the third constant region of mouse heavy chain IgG2a allopeptide gamma 2ab, which mimics a corneal Ag implicated in autoimmune keratitis. In a competition assay performed in vitro using reference hybridomas of known MHC class II restriction, both retro-inverso analogues bound (although more weakly in our test) to I-Ad and/or I-Ed class II molecules. However, in both cases, this lower affinity was apparently largely compensated in vivo, as a T cell response (with IL-2 secretion), equivalent to that obtained with the wild-type peptides, was observed following immunization of BALB/c mice with the retro-inverso analogues. Moreover, these T cells proliferated and produced IL-2 in response to the cognate peptides. It is concluded that the T cell receptors of T cells primed in vivo with the retro-inverso analogues readily cross-react with parent and retro-inverso analogue-MHC complexes. The approach of using pseudopeptides containing changes involving the backbone, and not the orientation of side chains, may thus be promising to design potent immunogens for class II-restricted T cells.
1996
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.
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, 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.
1991
Hoffmann Jules A, Joosse J
Chinless wonders. Molecular Aspects of Invertebrate Hormones. A Jacques Monod Conference sponsored by the Centre National de la Recherche Scientifique, Roscoff, France, October 14-19, 1990 Article de journal
Dans: New Biol., vol. 3, no. 4, p. 336–340, 1991, ISSN: 1043-4674.
BibTeX | Étiquettes: Animals, Crustacea, Ecdysone, hoffmann, insects, Invertebrate Hormones, Juvenile Hormones, M3i, Neuropeptides, Receptors, Snails, Steroid
@article{hoffmann_chinless_1991,
title = {Chinless wonders. Molecular Aspects of Invertebrate Hormones. A Jacques Monod Conference sponsored by the Centre National de la Recherche Scientifique, Roscoff, France, October 14-19, 1990},
author = {Jules A Hoffmann and J Joosse},
issn = {1043-4674},
year = {1991},
date = {1991-04-01},
journal = {New Biol.},
volume = {3},
number = {4},
pages = {336--340},
keywords = {Animals, Crustacea, Ecdysone, hoffmann, insects, Invertebrate Hormones, Juvenile Hormones, M3i, Neuropeptides, Receptors, Snails, Steroid},
pubstate = {published},
tppubtype = {article}
}