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2012 |
Lemaitre, Bruno; Nicolas, Emmanuelle; Michaut, Lydia; Reichhart, Jean-Marc; Hoffmann, Jules A Pillars article: the dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996. 86: 973-983 Article de journal J. Immunol., 188 (11), p. 5210–5220, 2012, ISSN: 1550-6606. Résumé | BibTeX | Étiquettes: Animals, Antifungal Agents, Developmental, DNA-Binding Proteins, Gene Expression Regulation, history, hoffmann, M3i, Multigene Family, Mycoses, Phosphoproteins, reichhart, Toll-Like Receptors @article{lemaitre_pillars_2012, title = {Pillars article: the dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996. 86: 973-983}, author = {Bruno Lemaitre and Emmanuelle Nicolas and Lydia Michaut and Jean-Marc Reichhart and Jules A Hoffmann}, issn = {1550-6606}, year = {2012}, date = {2012-06-01}, journal = {J. Immunol.}, volume = {188}, number = {11}, pages = {5210--5220}, 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 regulatory gene cassette, 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, Developmental, DNA-Binding Proteins, Gene Expression Regulation, history, hoffmann, M3i, Multigene Family, Mycoses, Phosphoproteins, reichhart, 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 regulatory gene cassette, 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. |
2009 |
Garrett, Matthew; Fullaondo, Ane; Troxler, Laurent; Micklem, Gos; Gubb, David Identification and analysis of serpin-family genes by homology and synteny across the 12 sequenced Drosophilid genomes Article de journal BMC Genomics, 10 , p. 489, 2009, ISSN: 1471-2164. Résumé | Liens | BibTeX | Étiquettes: Animals, bioinformatic, Comparative Genomic Hybridization, Conserved Sequence, DNA, Drosophilidae, Evolution, Genome, Insect, Molecular, Multigene Family, Sequence Alignment, Sequence Analysis, Serpins, Synteny @article{garrett_identification_2009, title = {Identification and analysis of serpin-family genes by homology and synteny across the 12 sequenced Drosophilid genomes}, author = {Matthew Garrett and Ane Fullaondo and Laurent Troxler and Gos Micklem and David Gubb}, doi = {10.1186/1471-2164-10-489}, issn = {1471-2164}, year = {2009}, date = {2009-01-01}, journal = {BMC Genomics}, volume = {10}, pages = {489}, abstract = {BACKGROUND: The Drosophila melanogaster genome contains 29 serpin genes, 12 as single transcripts and 17 within 6 gene clusters. Many of these serpins have a conserved "hinge" motif characteristic of active proteinase inhibitors. However, a substantial proportion (42%) lacks this motif and represents non-inhibitory serpin-fold proteins of unknown function. Currently, it is not known whether orthologous, inhibitory serpin genes retain the same target proteinase specificity within the Drosophilid lineage, nor whether they give rise to non-inhibitory serpin-fold proteins or other, more diverged, proteins. RESULTS: We collated 188 orthologues to the D. melanogaster serpins from the other 11 Drosophilid genomes and used synteny to find further family members, raising the total to 226, or 71% of the number of orthologues expected assuming complete conservation across all 12 Drosophilid species. In general the sequence constraints on the serpin-fold itself are loose. The critical Reactive Centre Loop (RCL) sequence, including the target proteinase cleavage site, is strongly conserved in inhibitory serpins, although there are 3 exceptional sets of orthologues in which the evolutionary constraints are looser. Conversely, the RCL of non-inhibitory serpin orthologues is less conserved, with 3 exceptions that presumably bind to conserved partner molecules. We derive a consensus hinge motif, for Drosophilid inhibitory serpins, which differs somewhat from that of the vertebrate consensus. Three gene clusters appear to have originated in the melanogaster subgroup, Spn28D, Spn77B and Spn88E, each containing one inhibitory serpin orthologue that is present in all Drosophilids. In addition, the Spn100A transcript appears to represent a novel serpin-derived fold. CONCLUSION: In general, inhibitory serpins rarely change their range of proteinase targets, except by a duplication/divergence mechanism. Non-inhibitory serpins appear to derive from inhibitory serpins, but not the reverse. The conservation of different family members varied widely across the 12 sequenced Drosophilid genomes. An approach considering synteny as well as homology was important to find the largest set of orthologues.}, keywords = {Animals, bioinformatic, Comparative Genomic Hybridization, Conserved Sequence, DNA, Drosophilidae, Evolution, Genome, Insect, Molecular, Multigene Family, Sequence Alignment, Sequence Analysis, Serpins, Synteny}, pubstate = {published}, tppubtype = {article} } BACKGROUND: The Drosophila melanogaster genome contains 29 serpin genes, 12 as single transcripts and 17 within 6 gene clusters. Many of these serpins have a conserved "hinge" motif characteristic of active proteinase inhibitors. However, a substantial proportion (42%) lacks this motif and represents non-inhibitory serpin-fold proteins of unknown function. Currently, it is not known whether orthologous, inhibitory serpin genes retain the same target proteinase specificity within the Drosophilid lineage, nor whether they give rise to non-inhibitory serpin-fold proteins or other, more diverged, proteins. RESULTS: We collated 188 orthologues to the D. melanogaster serpins from the other 11 Drosophilid genomes and used synteny to find further family members, raising the total to 226, or 71% of the number of orthologues expected assuming complete conservation across all 12 Drosophilid species. In general the sequence constraints on the serpin-fold itself are loose. The critical Reactive Centre Loop (RCL) sequence, including the target proteinase cleavage site, is strongly conserved in inhibitory serpins, although there are 3 exceptional sets of orthologues in which the evolutionary constraints are looser. Conversely, the RCL of non-inhibitory serpin orthologues is less conserved, with 3 exceptions that presumably bind to conserved partner molecules. We derive a consensus hinge motif, for Drosophilid inhibitory serpins, which differs somewhat from that of the vertebrate consensus. Three gene clusters appear to have originated in the melanogaster subgroup, Spn28D, Spn77B and Spn88E, each containing one inhibitory serpin orthologue that is present in all Drosophilids. In addition, the Spn100A transcript appears to represent a novel serpin-derived fold. CONCLUSION: In general, inhibitory serpins rarely change their range of proteinase targets, except by a duplication/divergence mechanism. Non-inhibitory serpins appear to derive from inhibitory serpins, but not the reverse. The conservation of different family members varied widely across the 12 sequenced Drosophilid genomes. An approach considering synteny as well as homology was important to find the largest set of orthologues. |
2006 |
Evans, J D; Aronstein, K; Chen, Y P; Hetru, Charles; Imler, Jean-Luc; Jiang, H; Kanost, M; Thompson, G J; Zou, Z; Hultmark, D Immune pathways and defence mechanisms in honey bees Apis mellifera Article de journal Insect Molecular Biology, 15 (5), p. 645–656, 2006, ISSN: 0962-1075. Résumé | Liens | BibTeX | Étiquettes: Animals, Bees, Carrier Proteins, Genome, imler, Immunity, Insect, Janus Kinases, M3i, Multigene Family, Serine Endopeptidases, Signal Transduction, STAT Transcription Factors, Toll-Like Receptors @article{evans_immune_2006, title = {Immune pathways and defence mechanisms in honey bees Apis mellifera}, author = {J D Evans and K Aronstein and Y P Chen and Charles Hetru and Jean-Luc Imler and H Jiang and M Kanost and G J Thompson and Z Zou and D Hultmark}, doi = {10.1111/j.1365-2583.2006.00682.x}, issn = {0962-1075}, year = {2006}, date = {2006-10-01}, journal = {Insect Molecular Biology}, volume = {15}, number = {5}, pages = {645--656}, abstract = {Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera. We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity. We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens.}, keywords = {Animals, Bees, Carrier Proteins, Genome, imler, Immunity, Insect, Janus Kinases, M3i, Multigene Family, Serine Endopeptidases, Signal Transduction, STAT Transcription Factors, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Social insects are able to mount both group-level and individual defences against pathogens. Here we focus on individual defences, by presenting a genome-wide analysis of immunity in a social insect, the honey bee Apis mellifera. We present honey bee models for each of four signalling pathways associated with immunity, identifying plausible orthologues for nearly all predicted pathway members. When compared to the sequenced Drosophila and Anopheles genomes, honey bees possess roughly one-third as many genes in 17 gene families implicated in insect immunity. We suggest that an implied reduction in immune flexibility in bees reflects either the strength of social barriers to disease, or a tendency for bees to be attacked by a limited set of highly coevolved pathogens. |
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 Gene expression patterns: GEP, 2 (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. |
Christophides, George K; Zdobnov, Evgeny; Barillas-Mury, Carolina; Birney, Ewan; Blandin, Stephanie A; Blass, Claudia; Brey, Paul T; Collins, Frank H; Danielli, Alberto; Dimopoulos, George; Hetru, Charles; Hoa, Ngo T; Hoffmann, Jules A; Kanzok, Stefan M; Letunic, Ivica; Levashina, Elena A; Loukeris, Thanasis G; Lycett, Gareth; Meister, Stephan; Michel, Kristin; Moita, Luis F; Müller, Hans-Michael; Osta, Mike A; Paskewitz, Susan M; Reichhart, Jean-Marc; Rzhetsky, Andrey; Troxler, Laurent; Vernick, Kenneth D; Vlachou, Dina; Volz, Jennifer; von Mering, Christian; Xu, Jiannong; Zheng, Liangbiao; Bork, Peer; Kafatos, Fotis C Immunity-related genes and gene families in Anopheles gambiae Article de journal Science, 298 (5591), p. 159–165, 2002, ISSN: 1095-9203. Résumé | Liens | BibTeX | Étiquettes: Alternative Splicing, Animals, Anopheles, Apoptosis, bacteria, bioinformatic, blandin, Catechol Oxidase, Computational Biology, Enzyme Precursors, Gene Expression Regulation, Genes, Genetic, Genome, hoffmann, Immunity, Innate, Insect, Insect Proteins, M3i, Multigene Family, Peptides, Phylogeny, Plasmodium, Protein Structure, reichhart, Selection, Serine Endopeptidases, Serpins, Signal Transduction, Tertiary @article{christophides_immunity-related_2002, title = {Immunity-related genes and gene families in Anopheles gambiae}, author = {George K Christophides and Evgeny Zdobnov and Carolina Barillas-Mury and Ewan Birney and Stephanie A Blandin and Claudia Blass and Paul T Brey and Frank H Collins and Alberto Danielli and George Dimopoulos and Charles Hetru and Ngo T Hoa and Jules A Hoffmann and Stefan M Kanzok and Ivica Letunic and Elena A Levashina and Thanasis G Loukeris and Gareth Lycett and Stephan Meister and Kristin Michel and Luis F Moita and Hans-Michael Müller and Mike A Osta and Susan M Paskewitz and Jean-Marc Reichhart and Andrey Rzhetsky and Laurent Troxler and Kenneth D Vernick and Dina Vlachou and Jennifer Volz and Christian von Mering and Jiannong Xu and Liangbiao Zheng and Peer Bork and Fotis C Kafatos}, url = {http://www.ncbi.nlm.nih.gov/pubmed/12364793}, doi = {10.1126/science.1077136}, issn = {1095-9203}, year = {2002}, date = {2002-10-01}, journal = {Science}, volume = {298}, number = {5591}, pages = {159--165}, abstract = {We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire.}, keywords = {Alternative Splicing, Animals, Anopheles, Apoptosis, bacteria, bioinformatic, blandin, Catechol Oxidase, Computational Biology, Enzyme Precursors, Gene Expression Regulation, Genes, Genetic, Genome, hoffmann, Immunity, Innate, Insect, Insect Proteins, M3i, Multigene Family, Peptides, Phylogeny, Plasmodium, Protein Structure, reichhart, Selection, Serine Endopeptidases, Serpins, Signal Transduction, Tertiary}, pubstate = {published}, tppubtype = {article} } We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire. |
2000 |
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 Proceedings of the National Academy of Sciences of the United States of America, 97 (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 Toll and Toll-like proteins: an ancient family of receptors signaling infection Article de journal Reviews in Immunogenetics, 2 (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. |
1990 |
Lagueux, Marie; Lwoff, L; Meister, Marie; Goltzené, F; Hoffmann, Jules A cDNAs from neurosecretory cells of brains of Locusta migratoria (Insecta, Orthoptera) encoding a novel member of the superfamily of insulins Article de journal Eur. J. Biochem., 187 (1), p. 249–254, 1990, ISSN: 0014-2956. Résumé | BibTeX | Étiquettes: Animals, Base Sequence, DNA, Genes, Grasshoppers, hoffmann, Humans, Insulin, M3i, Multigene Family, Nervous System, Neuropeptides, Neurosecretory Systems, Nucleic Acid, Nucleic Acid Hybridization, Oligonucleotide Probes, RNA, Sequence Homology @article{lagueux_cdnas_1990, title = {cDNAs from neurosecretory cells of brains of Locusta migratoria (Insecta, Orthoptera) encoding a novel member of the superfamily of insulins}, author = {Marie Lagueux and L Lwoff and Marie Meister and F Goltzené and Jules A Hoffmann}, issn = {0014-2956}, year = {1990}, date = {1990-01-01}, journal = {Eur. J. Biochem.}, volume = {187}, number = {1}, pages = {249--254}, abstract = {From neurohaemal lobes of corpora cardiaca of Locusta migratoria a 5-kDa peptide has been isolated and its sequence established [see the accompanying paper, by Hietter et al. (1990) Eur. J. Biochem. 187, 241-247]. We have designed oligonucleotide probes from the peptide sequence of this molecule and screened a library prepared from mRNA of the neurosecretory cell region of the brain of this insect. Several positive cDNAs were isolated, the combined nucleotide sequences of which predict a large precursor of 145 residues (15770 Da) containing the newly isolated 5-kDa peptide. The peptide is flanked by regions homologous to the A and B chains of the superfamily of insulins. The overall organization of the precursor is as follows: signal peptide/domain homologous to the B chain of insulins/C (connecting)-peptide (corresponding to the newly isolated 5-kDa peptide)/domain homologous to the A chain of insulins. The numbers and relative positions of the cysteines of the Locusta peptide are equivalent to those of the other members of the insulin superfamily and most of the hydrophobic core residues are conserved.}, keywords = {Animals, Base Sequence, DNA, Genes, Grasshoppers, hoffmann, Humans, Insulin, M3i, Multigene Family, Nervous System, Neuropeptides, Neurosecretory Systems, Nucleic Acid, Nucleic Acid Hybridization, Oligonucleotide Probes, RNA, Sequence Homology}, pubstate = {published}, tppubtype = {article} } From neurohaemal lobes of corpora cardiaca of Locusta migratoria a 5-kDa peptide has been isolated and its sequence established [see the accompanying paper, by Hietter et al. (1990) Eur. J. Biochem. 187, 241-247]. We have designed oligonucleotide probes from the peptide sequence of this molecule and screened a library prepared from mRNA of the neurosecretory cell region of the brain of this insect. Several positive cDNAs were isolated, the combined nucleotide sequences of which predict a large precursor of 145 residues (15770 Da) containing the newly isolated 5-kDa peptide. The peptide is flanked by regions homologous to the A and B chains of the superfamily of insulins. The overall organization of the precursor is as follows: signal peptide/domain homologous to the B chain of insulins/C (connecting)-peptide (corresponding to the newly isolated 5-kDa peptide)/domain homologous to the A chain of insulins. The numbers and relative positions of the cysteines of the Locusta peptide are equivalent to those of the other members of the insulin superfamily and most of the hydrophobic core residues are conserved. |
Wicker, C; Reichhart, Jean-Marc; Hoffmann, Danièle; Hultmark, D; Samakovlis, C; Hoffmann, Jules A Insect immunity. Characterization of a Drosophila cDNA encoding a novel member of the diptericin family of immune peptides Article de journal J. Biol. Chem., 265 (36), p. 22493–22498, 1990, ISSN: 0021-9258. Résumé | BibTeX | Étiquettes: Animals, Anti-Bacterial Agents, Base Sequence, Cloning, Diptera, DNA, Escherichia coli, hoffmann, Insect Hormones, Insect Proteins, M3i, Molecular, Multigene Family, Nucleic Acid, Oligonucleotide Probes, reichhart, Sequence Homology @article{wicker_insect_1990, title = {Insect immunity. Characterization of a Drosophila cDNA encoding a novel member of the diptericin family of immune peptides}, author = {C Wicker and Jean-Marc Reichhart and Danièle Hoffmann and D Hultmark and C Samakovlis and Jules A Hoffmann}, issn = {0021-9258}, year = {1990}, date = {1990-01-01}, journal = {J. Biol. Chem.}, volume = {265}, number = {36}, pages = {22493--22498}, abstract = {Drosophila shows an immune response when challenged by injection of low doses of bacteria. To date, the molecules involved in this immune reaction have remained elusive, with the exception of cecropins (4-kDa antibacterial peptides initially isolated from the moth Hyalophora cecropia) for which three closely related genes have been characterized recently. We report the molecular cloning and sequencing of a cDNA from a library of immune Drosophila which encodes a novel member of the family of diptericins (9-kDa antibacterial peptides initially isolated from the fly Phormia terranovae). Transcripts for the Drosophila diptericin are detected 2 h after injection of bacteria. They are apparently derived from a single gene mapping at position 56 A on the right arm of the second chromosome. We discuss the existence of a distant relationship between the diptericins and two other groups of anti-bacterial insect proteins, the attacins, and the sarcotoxins II.}, keywords = {Animals, Anti-Bacterial Agents, Base Sequence, Cloning, Diptera, DNA, Escherichia coli, hoffmann, Insect Hormones, Insect Proteins, M3i, Molecular, Multigene Family, Nucleic Acid, Oligonucleotide Probes, reichhart, Sequence Homology}, pubstate = {published}, tppubtype = {article} } Drosophila shows an immune response when challenged by injection of low doses of bacteria. To date, the molecules involved in this immune reaction have remained elusive, with the exception of cecropins (4-kDa antibacterial peptides initially isolated from the moth Hyalophora cecropia) for which three closely related genes have been characterized recently. We report the molecular cloning and sequencing of a cDNA from a library of immune Drosophila which encodes a novel member of the family of diptericins (9-kDa antibacterial peptides initially isolated from the fly Phormia terranovae). Transcripts for the Drosophila diptericin are detected 2 h after injection of bacteria. They are apparently derived from a single gene mapping at position 56 A on the right arm of the second chromosome. We discuss the existence of a distant relationship between the diptericins and two other groups of anti-bacterial insect proteins, the attacins, and the sarcotoxins II. |