Publications
2014
Goto Akira, Fukuyama Hidehiro, Imler Jean-Luc, Hoffmann Jules A
The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response Article de journal
Dans: The Journal of Biological Chemistry, vol. 289, no. 30, p. 20470–20476, 2014, ISSN: 1083-351X.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Line, Chromatin Assembly and Disassembly, Epistasis, Escherichia coli, Escherichia coli Infections, Genetic, hoffmann, imler, Immunity, Innate, M3i, NF-kappa B, Repressor Proteins, Signal Transduction, Transcription Factors
@article{goto_chromatin_2014,
title = {The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response},
author = {Akira Goto and Hidehiro Fukuyama and Jean-Luc Imler and Jules A Hoffmann},
doi = {10.1074/jbc.C114.553719},
issn = {1083-351X},
year = {2014},
date = {2014-07-01},
journal = {The Journal of Biological Chemistry},
volume = {289},
number = {30},
pages = {20470--20476},
abstract = {The host defense of the model organism Drosophila is under the control of two major signaling cascades controlling transcription factors of the NF-B family, the Toll and the immune deficiency (IMD) pathways. The latter shares extensive similarities with the mammalian TNF-R pathway and was initially discovered for its role in anti-Gram-negative bacterial reactions. A previous interactome study from this laboratory reported that an unexpectedly large number of proteins are binding to the canonical components of the IMD pathway. Here, we focus on DNA methyltransferase-associated protein 1 (DMAP1), which this study identified as an interactant of Relish, a Drosophila transcription factor reminiscent of the mammalian p105 NF-B protein. We show that silencing of DMAP1 expression both in S2 cells and in flies results in a significant reduction of Escherichia coli-induced expression of antimicrobial peptides. Epistatic analysis indicates that DMAP1 acts in parallel or downstream of Relish. Co-immunoprecipitation experiments further reveal that, in addition to Relish, DMAP1 also interacts with Akirin and the Brahma-associated protein 55 kDa (BAP55). Taken together, these results reveal that DMAP1 is a novel nuclear modulator of the IMD pathway, possibly acting at the level of chromatin remodeling.},
keywords = {Animals, Cell Line, Chromatin Assembly and Disassembly, Epistasis, Escherichia coli, Escherichia coli Infections, Genetic, hoffmann, imler, Immunity, Innate, M3i, NF-kappa B, Repressor Proteins, Signal Transduction, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
2006
Chen Li-Ying, Wang Juinn-Chin, Hyvert Yann, Lin Hui-Ping, Perrimon Norbert, Imler Jean-Luc, Hsu Jui-Chou
Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo Article de journal
Dans: Current biology: CB, vol. 16, no. 12, p. 1183–1193, 2006, ISSN: 0960-9822.
Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Animals, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, imler, Immunity, Immunologic, Innate, M3i, Models, Mutation, Nonmammalian, Phenotype, Phosphoproteins, Receptors, Signal Transducing, Toll-Like Receptors, Transcription Factors, Zinc Fingers
@article{chen_weckle_2006,
title = {Weckle is a zinc finger adaptor of the toll pathway in dorsoventral patterning of the Drosophila embryo},
author = {Li-Ying Chen and Juinn-Chin Wang and Yann Hyvert and Hui-Ping Lin and Norbert Perrimon and Jean-Luc Imler and Jui-Chou Hsu},
doi = {10.1016/j.cub.2006.05.050},
issn = {0960-9822},
year = {2006},
date = {2006-06-01},
journal = {Current biology: CB},
volume = {16},
number = {12},
pages = {1183--1193},
abstract = {BACKGROUND: The Drosophila Toll pathway takes part in both establishment of the embryonic dorsoventral axis and induction of the innate immune response in adults. Upon activation by the cytokine Spätzle, Toll interacts with the adaptor proteins DmMyD88 and Tube and the kinase Pelle and triggers degradation of the inhibitor Cactus, thus allowing the nuclear translocation of the transcription factor Dorsal/Dif. weckle (wek) was previously identified as a new dorsal group gene that encodes a putative zinc finger transcription factor. However, its role in the Toll pathway was unknown. RESULTS: Here, we isolated new wek alleles and demonstrated that cactus is epistatic to wek, which in turn is epistatic to Toll. Consistent with this, Wek localizes to the plasma membrane of embryos, independently of Toll signaling. Wek homodimerizes and associates with Toll. Moreover, Wek binds to and localizes DmMyD88 to the plasma membrane. Thus, Wek acts as an adaptor to assemble/stabilize a Toll/Wek/DmMyD88/Tube complex. Remarkably, unlike the DmMyD88/tube/pelle/cactus gene cassette of the Toll pathway, wek plays a minimal role, if any, in the immune defense against Gram-positive bacteria and fungi. CONCLUSIONS: We conclude that Wek is an adaptor to link Toll and DmMyD88 and is required for efficient recruitment of DmMyD88 to Toll. Unexpectedly, wek is dispensable for innate immune response, thus revealing differences in the Toll-mediated activation of Dorsal in the embryo and Dif in the fat body of adult flies.},
keywords = {Adaptor Proteins, Animals, Antigens, Biological, Body Patterning, Cell Membrane, Differentiation, dimerization, DNA-Binding Proteins, Embryo, Epistasis, Genetic, imler, Immunity, Immunologic, Innate, M3i, Models, Mutation, Nonmammalian, Phenotype, Phosphoproteins, Receptors, Signal Transducing, Toll-Like Receptors, Transcription Factors, Zinc Fingers},
pubstate = {published},
tppubtype = {article}
}
2003
Goto Akira, Blandin Stéphanie A, Royet Julien, Reichhart Jean-Marc, Levashina Elena A
Silencing of Toll pathway components by direct injection of double-stranded RNA into Drosophila adult flies Article de journal
Dans: Nucleic Acids Res., vol. 31, no. 22, p. 6619–6623, 2003, ISSN: 1362-4962.
Résumé | BibTeX | Étiquettes: Animals, blandin, Cell Surface, Double-Stranded, Epistasis, Female, Genetic, Green Fluorescent Proteins, Homeodomain Proteins, Luminescent Proteins, M3i, Phenotype, Receptors, reichhart, RNA, RNA Interference, Serpins, Signal Transduction, Time Factors, Toll-Like Receptors, Transcription Factors
@article{goto_silencing_2003,
title = {Silencing of Toll pathway components by direct injection of double-stranded RNA into Drosophila adult flies},
author = {Akira Goto and Stéphanie A Blandin and Julien Royet and Jean-Marc Reichhart and Elena A Levashina},
issn = {1362-4962},
year = {2003},
date = {2003-11-01},
journal = {Nucleic Acids Res.},
volume = {31},
number = {22},
pages = {6619--6623},
abstract = {Double-stranded RNA (dsRNA) gene interference is an efficient method to silence gene expression in a sequence-specific manner. Here we show that the direct injection of dsRNA can be used in adult Drosophila flies to disrupt function of endogenous genes in vivo. As a proof of principle, we have used this method to silence components of a major signaling cascade, the Toll pathway, which controls fruit fly resistance to fungal and Gram-positive bacterial infections. We demonstrate that the knockout is efficient only if dsRNA is injected in 4- or more day-old flies and that it lasts for at least 1 week. Furthermore, we report dsRNA-based epistatic gene analysis via injection of a mixture of two dsRNAs and propose that injection of dsRNA represents a powerful method for rapid functional analysis of genes in Drosophila melanogaster adults, particularly of those whose mutations are lethal during development.},
keywords = {Animals, blandin, Cell Surface, Double-Stranded, Epistasis, Female, Genetic, Green Fluorescent Proteins, Homeodomain Proteins, Luminescent Proteins, M3i, Phenotype, Receptors, reichhart, RNA, RNA Interference, Serpins, Signal Transduction, Time Factors, Toll-Like Receptors, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
2002
Gottar Marie, Gobert Vanessa, Michel Tatiana, Belvin Marcia, Duyk Geoffrey, Hoffmann Jules A, Ferrandon Dominique, Royet Julien
The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein Article de journal
Dans: Nature, vol. 416, p. 640–644, 2002, ISBN: 0028-0836.
Résumé | Liens | BibTeX | Étiquettes: Animal, Anti-Infective Agents/metabolism, Carrier Proteins/biosynthesis/genetics/*immunology, Drosophila melanogaster/genetics/*immunology/*microbiology, Drosophila Proteins/genetics/metabolism, Epistasis, Female, ferrandon, Genes, Genetic, Genetic Predisposition to Disease, Gram-Negative Bacteria/*immunology/physiology, hoffmann, Human, Insect/genetics, M3i, Messenger/genetics/metabolism, Mutation, Non-U.S. Gov't, P.H.S., Phenotype, RNA, Signal Transduction, Support, Survival Rate, Transgenes/genetics, U.S. Gov't
@article{gottar_drosophila_2002b,
title = {The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein},
author = {Marie Gottar and Vanessa Gobert and Tatiana Michel and Marcia Belvin and Geoffrey Duyk and Jules A Hoffmann and Dominique Ferrandon and Julien Royet},
doi = {10.1038/nature734},
isbn = {0028-0836},
year = {2002},
date = {2002-03-01},
journal = {Nature},
volume = {416},
pages = {640--644},
abstract = {The antimicrobial defence of Drosophila relies largely on the challenge-induced synthesis of an array of potent antimicrobial peptides by the fat body. The defence against Gram-positive bacteria and natural fungal infections is mediated by the Toll signalling pathway, whereas defence against Gram-negative bacteria is dependent on the Immune deficiency (IMD) pathway. Loss-of-function mutations in either pathway reduce the resistance to corresponding infections. The link between microbial infections and activation of these two pathways has remained elusive. The Toll pathway is activated by Gram-positive bacteria through a circulating Peptidoglycan recognition protein (PGRP-SA). PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members. Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections. By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene. The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila.},
keywords = {Animal, Anti-Infective Agents/metabolism, Carrier Proteins/biosynthesis/genetics/*immunology, Drosophila melanogaster/genetics/*immunology/*microbiology, Drosophila Proteins/genetics/metabolism, Epistasis, Female, ferrandon, Genes, Genetic, Genetic Predisposition to Disease, Gram-Negative Bacteria/*immunology/physiology, hoffmann, Human, Insect/genetics, M3i, Messenger/genetics/metabolism, Mutation, Non-U.S. Gov't, P.H.S., Phenotype, RNA, Signal Transduction, Support, Survival Rate, Transgenes/genetics, U.S. Gov't},
pubstate = {published},
tppubtype = {article}
}
Tauszig-Delamasure Servane, Bilak Hana, Capovilla Maria, Hoffmann Jules A, Imler Jean-Luc
Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections 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}
}