Publications
2003 |
|
Articles de journaux |
|
| 22. | Hetru, Charles; Troxler, Laurent; Hoffmann, Jules A Drosophila melanogaster antimicrobial defense Article de journal J. Infect. Dis., 187 Suppl 2 , p. S327–334, 2003, ISSN: 0022-1899. Résumé | Liens | BibTeX | Étiquettes: Animal, Bacterial Infections, bioinformatic, Immunity, Innate, Mycoses, Parasitic Diseases, Peptides, Signal Transduction @article{hetru_drosophila_2003, title = {Drosophila melanogaster antimicrobial defense}, author = { Charles Hetru and Laurent Troxler and Jules A. Hoffmann}, doi = {10.1086/374758}, issn = {0022-1899}, year = {2003}, date = {2003-06-01}, journal = {J. Infect. Dis.}, volume = {187 Suppl 2}, pages = {S327--334}, abstract = {The Drosophila melanogaster host defense is complex but remarkably efficient. It is a multifaceted response to a variety of fungal, bacterial, and parasitic invaders. Current knowledge is discussed on recognition of infectious microorganisms and on the activation of intracellular signaling cascades that concur with the expression of numerous immune-responsive genes, among which, to date, the most prominent appear to encode potent antimicrobial peptides.}, keywords = {Animal, Bacterial Infections, bioinformatic, Immunity, Innate, Mycoses, Parasitic Diseases, Peptides, Signal Transduction}, pubstate = {published}, tppubtype = {article} } The Drosophila melanogaster host defense is complex but remarkably efficient. It is a multifaceted response to a variety of fungal, bacterial, and parasitic invaders. Current knowledge is discussed on recognition of infectious microorganisms and on the activation of intracellular signaling cascades that concur with the expression of numerous immune-responsive genes, among which, to date, the most prominent appear to encode potent antimicrobial peptides. |
2002 |
|
Articles de journaux |
|
| 21. | 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, Anopheles, Apoptosis, Bacteria, bioinformatic, Catechol Oxidase, Computational Biology, Enzyme Precursors, Gene Expression Regulation, Genes, Genetic, Genome, Immunity, Innate, Insect, Insect Proteins, Multigene Family, Peptides, Phylogeny, Plasmodium, Protein Structure, 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, Anopheles, Apoptosis, Bacteria, bioinformatic, Catechol Oxidase, Computational Biology, Enzyme Precursors, Gene Expression Regulation, Genes, Genetic, Genome, Immunity, Innate, Insect, Insect Proteins, Multigene Family, Peptides, Phylogeny, Plasmodium, Protein Structure, 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. |
2001 |
|
Articles de journaux |
|
| 20. | Lamberty, M; Zachary, Daniel; Lanot, R; Bordereau, C; Robert, A; Hoffmann, Jules A; Bulet, Philippe Insect immunity. Constitutive expression of a cysteine-rich antifungal and a linear antibacterial peptide in a termite insect. Article de journal J. Biol. Chem., 276 (6), p. 4085–4092, 2001, ISSN: 0021-9258. Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Anti-Bacterial Agents, Antifungal Agents, Base Sequence, Chromatography, Cysteine, DNA Primers, High Pressure Liquid, Immunohistochemistry, Isoptera, Peptides, Protein Conformation, Recombinant Proteins, Sequence Homology @article{lamberty_insect_2001, title = {Insect immunity. Constitutive expression of a cysteine-rich antifungal and a linear antibacterial peptide in a termite insect.}, author = { M. Lamberty and Daniel Zachary and R. Lanot and C. Bordereau and A. Robert and Jules A. Hoffmann and Philippe Bulet}, doi = {10.1074/jbc.M002998200}, issn = {0021-9258}, year = {2001}, date = {2001-02-01}, journal = {J. Biol. Chem.}, volume = {276}, number = {6}, pages = {4085--4092}, abstract = {Two novel antimicrobial peptides, which we propose to name termicin and spinigerin, have been isolated from the fungus-growing termite Pseudacanthotermes spiniger (heterometabole insect, Isoptera). Termicin is a 36-amino acid residue antifungal peptide, with six cysteines arranged in a disulfide array similar to that of insect defensins. In contrast to most insect defensins, termicin is C-terminally amidated. Spinigerin consists of 25 amino acids and is devoid of cysteines. It is active against bacteria and fungi. Termicin and spinigerin show no obvious sequence similarities with other peptides. Termicin is constitutively present in hemocyte granules and in salivary glands. The presence of termicin and spinigerin in unchallenged termites contrasts with observations in evolutionary recent insects or insects undergoing complete metamorphosis, in which antimicrobial peptides are induced in the fat body and released into the hemolymph after septic injury.}, keywords = {Amino Acid, Anti-Bacterial Agents, Antifungal Agents, Base Sequence, Chromatography, Cysteine, DNA Primers, High Pressure Liquid, Immunohistochemistry, Isoptera, Peptides, Protein Conformation, Recombinant Proteins, Sequence Homology}, pubstate = {published}, tppubtype = {article} } Two novel antimicrobial peptides, which we propose to name termicin and spinigerin, have been isolated from the fungus-growing termite Pseudacanthotermes spiniger (heterometabole insect, Isoptera). Termicin is a 36-amino acid residue antifungal peptide, with six cysteines arranged in a disulfide array similar to that of insect defensins. In contrast to most insect defensins, termicin is C-terminally amidated. Spinigerin consists of 25 amino acids and is devoid of cysteines. It is active against bacteria and fungi. Termicin and spinigerin show no obvious sequence similarities with other peptides. Termicin is constitutively present in hemocyte granules and in salivary glands. The presence of termicin and spinigerin in unchallenged termites contrasts with observations in evolutionary recent insects or insects undergoing complete metamorphosis, in which antimicrobial peptides are induced in the fat body and released into the hemolymph after septic injury. |
2000 |
|
Articles de journaux |
|
| 19. | 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, Anti-Bacterial Agents, Blotting, Cell Line, Cell Surface, 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, Anti-Bacterial Agents, Blotting, Cell Line, Cell Surface, 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. |
1999 |
|
Articles de journaux |
|
| 18. | 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 Science, 285 (5435), p. 1917–1919, 1999, ISSN: 0036-8075. Résumé | BibTeX | Étiquettes: Antifungal Agents, Antimicrobial Cationic Peptides, Body Patterning, Cell Surface, Escherichia coli, Genes, Hemolymph, Insect, Insect Proteins, Membrane Glycoproteins, Micrococcus luteus, Mutagenesis, Peptides, Receptors, Recombinant Fusion Proteins, 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 = {Antifungal Agents, Antimicrobial Cationic Peptides, Body Patterning, Cell Surface, Escherichia coli, Genes, Hemolymph, Insect, Insect Proteins, Membrane Glycoproteins, Micrococcus luteus, Mutagenesis, Peptides, Receptors, Recombinant Fusion Proteins, 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. |
1998 |
|
Articles de journaux |
|
| 17. | Uttenweiler-Joseph, S; Moniatte, M; Lagueux, Marie; Dorsselaer, Van A; Hoffmann, Jules A; Bulet, Philippe Differential display of peptides induced during the immune response of Drosophila: a matrix-assisted laser desorption ionization time-of-flight mass spectrometry study Article de journal Proc. Natl. Acad. Sci. U.S.A., 95 (19), p. 11342–11347, 1998, ISSN: 0027-8424. Résumé | BibTeX | Étiquettes: Bacteria, Chromatography, Cloning, Hemolymph, High Pressure Liquid, Immunity, Insect Proteins, Mass, Matrix-Assisted Laser Desorption-Ionization, Messenger, Molecular, Peptides, Protein Precursors, RNA, Sequence Analysis, Spectrometry, Time Factors @article{uttenweiler-joseph_differential_1998, title = {Differential display of peptides induced during the immune response of Drosophila: a matrix-assisted laser desorption ionization time-of-flight mass spectrometry study}, author = { S. Uttenweiler-Joseph and M. Moniatte and Marie Lagueux and A. Van Dorsselaer and Jules A. Hoffmann and Philippe Bulet}, issn = {0027-8424}, year = {1998}, date = {1998-09-01}, journal = {Proc. Natl. Acad. Sci. U.S.A.}, volume = {95}, number = {19}, pages = {11342--11347}, abstract = {We have developed an approach based on a differential mass spectrometric analysis to detect molecules induced during the immune response of Drosophila, regardless of their biological activities. For this, we have applied directly matrix-assisted laser desorption/ionization MS to hemolymph samples from individual flies before and after an immune challenge. This method provided precise information on the molecular masses of immune-induced molecules and allowed the detection, in the molecular range of 1.5-11 kDa, of 24 Drosophila immune-induced molecules (DIMs). These molecules are all peptides, and four correspond to already characterized antimicrobial peptides. We have further analyzed the induction of the various peptides by immune challenge in wild-type flies and in mutants with a compromised antimicrobial response. We also describe a methodology combining matrix-assisted laser desorption ionization time-of-flight MS, HPLC, and Edman degradation, which yielded the peptide sequence of three of the DIMs. Finally, molecular cloning and Northern blot analyses revealed that one of the DIMs is produced as a prepropeptide and is inducible on a bacterial challenge.}, keywords = {Bacteria, Chromatography, Cloning, Hemolymph, High Pressure Liquid, Immunity, Insect Proteins, Mass, Matrix-Assisted Laser Desorption-Ionization, Messenger, Molecular, Peptides, Protein Precursors, RNA, Sequence Analysis, Spectrometry, Time Factors}, pubstate = {published}, tppubtype = {article} } We have developed an approach based on a differential mass spectrometric analysis to detect molecules induced during the immune response of Drosophila, regardless of their biological activities. For this, we have applied directly matrix-assisted laser desorption/ionization MS to hemolymph samples from individual flies before and after an immune challenge. This method provided precise information on the molecular masses of immune-induced molecules and allowed the detection, in the molecular range of 1.5-11 kDa, of 24 Drosophila immune-induced molecules (DIMs). These molecules are all peptides, and four correspond to already characterized antimicrobial peptides. We have further analyzed the induction of the various peptides by immune challenge in wild-type flies and in mutants with a compromised antimicrobial response. We also describe a methodology combining matrix-assisted laser desorption ionization time-of-flight MS, HPLC, and Edman degradation, which yielded the peptide sequence of three of the DIMs. Finally, molecular cloning and Northern blot analyses revealed that one of the DIMs is produced as a prepropeptide and is inducible on a bacterial challenge. |
| 16. | Bulet, Philippe; Uttenweiler-Joseph, S; Moniatte, M; Dorsselaer, Van A; Hoffmann, Jules A Differential display of peptides induced during the immune response of Drosophila: a matrix-assisted laser desorption ionization time-of-flight mass spectrometry study Article de journal J. Protein Chem., 17 (6), p. 528–529, 1998, ISSN: 0277-8033. BibTeX | Étiquettes: Anti-Infective Agents, Mass, Matrix-Assisted Laser Desorption-Ionization, Peptide Biosynthesis, Peptides, Spectrometry @article{bulet_differential_1998, title = {Differential display of peptides induced during the immune response of Drosophila: a matrix-assisted laser desorption ionization time-of-flight mass spectrometry study}, author = {Philippe Bulet and S. Uttenweiler-Joseph and M. Moniatte and A. Van Dorsselaer and Jules A. Hoffmann}, issn = {0277-8033}, year = {1998}, date = {1998-08-01}, journal = {J. Protein Chem.}, volume = {17}, number = {6}, pages = {528--529}, keywords = {Anti-Infective Agents, Mass, Matrix-Assisted Laser Desorption-Ionization, Peptide Biosynthesis, Peptides, Spectrometry}, pubstate = {published}, tppubtype = {article} } |
| 15. | Levashina, Elena A; Ohresser, S; Lemaitre, Bruno; Imler, Jean-Luc Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowin Article de journal Journal of Molecular Biology, 278 (3), p. 515–527, 1998, ISSN: 0022-2836. Résumé | Liens | BibTeX | Étiquettes: Anti-Infective Agents, Antimicrobial Cationic Peptides, Base Sequence, Cloning, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Glycopeptides, Insect, Insect Proteins, Larva, Molecular, Mutation, Peptides, Promoter Regions, Recombinant Fusion Proteins, Reporter, Restriction Mapping, Transcription @article{levashina_two_1998, title = {Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowin}, author = { Elena A. Levashina and S. Ohresser and Bruno Lemaitre and Jean-Luc Imler}, doi = {10.1006/jmbi.1998.1705}, issn = {0022-2836}, year = {1998}, date = {1998-01-01}, journal = {Journal of Molecular Biology}, volume = {278}, number = {3}, pages = {515--527}, abstract = {Metchnikowin is a recently discovered proline-rich peptide from Drosophila with antibacterial and antifungal properties. Like most other antimicrobial peptides from insects, its expression is immune-inducible. Here we present evidence that induction of metchnikowin gene expression can be mediated either by the TOLL pathway or by the imd gene product. We show that the gene remains inducible in Toll-deficient mutants, in which the antifungal response is blocked, as well as in imd mutants, which fail to mount an antibacterial response. However, in Toll-deficient;imd double mutants, metchnikowin gene expression can no longer be detected after immune challenge. Our results suggest that expression of this peptide with dual activity can be triggered by signals generated by either bacterial or fungal infection. Cloning of the metchnikowin gene revealed the presence in the 5' flanking region of several putative cis-regulatory motifs characterized in the promoters of insect immune genes: namely, Rel sites, GATA motifs, interferon consensus response elements and NF-IL6 response elements. Establishment of transgenic fly lines in which the GFP reporter gene was placed under the control of 1.5 kb of metchnikowin gene upstream sequences indicates that this fragment is able to confer full immune inducibility and tissue specificity of expression on the transgene.}, keywords = {Anti-Infective Agents, Antimicrobial Cationic Peptides, Base Sequence, Cloning, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Glycopeptides, Insect, Insect Proteins, Larva, Molecular, Mutation, Peptides, Promoter Regions, Recombinant Fusion Proteins, Reporter, Restriction Mapping, Transcription}, pubstate = {published}, tppubtype = {article} } Metchnikowin is a recently discovered proline-rich peptide from Drosophila with antibacterial and antifungal properties. Like most other antimicrobial peptides from insects, its expression is immune-inducible. Here we present evidence that induction of metchnikowin gene expression can be mediated either by the TOLL pathway or by the imd gene product. We show that the gene remains inducible in Toll-deficient mutants, in which the antifungal response is blocked, as well as in imd mutants, which fail to mount an antibacterial response. However, in Toll-deficient;imd double mutants, metchnikowin gene expression can no longer be detected after immune challenge. Our results suggest that expression of this peptide with dual activity can be triggered by signals generated by either bacterial or fungal infection. Cloning of the metchnikowin gene revealed the presence in the 5' flanking region of several putative cis-regulatory motifs characterized in the promoters of insect immune genes: namely, Rel sites, GATA motifs, interferon consensus response elements and NF-IL6 response elements. Establishment of transgenic fly lines in which the GFP reporter gene was placed under the control of 1.5 kb of metchnikowin gene upstream sequences indicates that this fragment is able to confer full immune inducibility and tissue specificity of expression on the transgene. |
1997 |
|
Articles de journaux |
|
| 14. | Lemaitre, Bruno; Reichhart, Jean-Marc ; Hoffmann, Jules A Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms Article de journal Proc. Natl. Acad. Sci. U.S.A., 94 (26), p. 14614–14619, 1997, ISSN: 0027-8424. Résumé | BibTeX | Étiquettes: Genes, Immunity, Insect, Peptides @article{lemaitre_drosophila_1997, title = {Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms}, author = { Bruno Lemaitre and Jean-Marc Reichhart and Jules A. Hoffmann}, issn = {0027-8424}, year = {1997}, date = {1997-12-01}, journal = {Proc. Natl. Acad. Sci. U.S.A.}, volume = {94}, number = {26}, pages = {14614--14619}, abstract = {Insects respond to microbial infection by the rapid and transient expression of several genes encoding potent antimicrobial peptides. Herein we demonstrate that this antimicrobial response of Drosophila is not aspecific but can discriminate between various classes of microorganisms. We first observe that the genes encoding antibacterial and antifungal peptides are differentially expressed after injection of distinct microorganisms. More strikingly, Drosophila that are naturally infected by entomopathogenic fungi exhibit an adapted response by producing only peptides with antifungal activities. This response is mediated through the selective activation of the Toll pathway.}, keywords = {Genes, Immunity, Insect, Peptides}, pubstate = {published}, tppubtype = {article} } Insects respond to microbial infection by the rapid and transient expression of several genes encoding potent antimicrobial peptides. Herein we demonstrate that this antimicrobial response of Drosophila is not aspecific but can discriminate between various classes of microorganisms. We first observe that the genes encoding antibacterial and antifungal peptides are differentially expressed after injection of distinct microorganisms. More strikingly, Drosophila that are naturally infected by entomopathogenic fungi exhibit an adapted response by producing only peptides with antifungal activities. This response is mediated through the selective activation of the Toll pathway. |
| 13. | Meister, Marie; Lemaitre, Bruno; Hoffmann, Jules A Antimicrobial peptide defense in Drosophila Article de journal Bioessays, 19 (11), p. 1019–1026, 1997, ISSN: 0265-9247. Résumé | Liens | BibTeX | Étiquettes: Anti-Infective Agents, Gene Expression Regulation, Genetic, Insect Proteins, Models, Peptides, Promoter Regions, Signal Transduction @article{meister_antimicrobial_1997, title = {Antimicrobial peptide defense in Drosophila}, author = { Marie Meister and Bruno Lemaitre and Jules A. Hoffmann}, doi = {10.1002/bies.950191112}, issn = {0265-9247}, year = {1997}, date = {1997-11-01}, journal = {Bioessays}, volume = {19}, number = {11}, pages = {1019--1026}, abstract = {Drosophila responds to a septic injury by the rapid synthesis of antimicrobial peptides. These molecules are predominantly produced by the fat body, a functional equivalent of mammalian liver, and are secreted into the hemolymph where their concentrations can reach up to 100 microM. Six distinct antibacterial peptides (plus isoforms) and one antifungal peptide have been characterized in Drosophila and their genes cloned. The induction of the gene encoding the antifungal peptide relies on the spätzle/Toll/cactus gene cassette, which is involved in the control of dorsoventral patterning in the embryo, and shows interesting structural and functional similarities with cytokine-induced activation of NF-kappa B in mammalian cells. An additional pathway, dependent on the as yet unidentified imd (for immune-deficiency) gene, is required for the full induction of the antibacterial peptide genes. Mutants deficient for the Toll and imd pathways exhibit a severely reduced survival to fungal and bacterial infections, respectively. Recent data on the molecular mechanisms underlying recognition of non-self are also discussed in this review.}, keywords = {Anti-Infective Agents, Gene Expression Regulation, Genetic, Insect Proteins, Models, Peptides, Promoter Regions, Signal Transduction}, pubstate = {published}, tppubtype = {article} } Drosophila responds to a septic injury by the rapid synthesis of antimicrobial peptides. These molecules are predominantly produced by the fat body, a functional equivalent of mammalian liver, and are secreted into the hemolymph where their concentrations can reach up to 100 microM. Six distinct antibacterial peptides (plus isoforms) and one antifungal peptide have been characterized in Drosophila and their genes cloned. The induction of the gene encoding the antifungal peptide relies on the spätzle/Toll/cactus gene cassette, which is involved in the control of dorsoventral patterning in the embryo, and shows interesting structural and functional similarities with cytokine-induced activation of NF-kappa B in mammalian cells. An additional pathway, dependent on the as yet unidentified imd (for immune-deficiency) gene, is required for the full induction of the antibacterial peptide genes. Mutants deficient for the Toll and imd pathways exhibit a severely reduced survival to fungal and bacterial infections, respectively. Recent data on the molecular mechanisms underlying recognition of non-self are also discussed in this review. |
1996 |
|
Articles de journaux |
|
| 12. | Ehret-Sabatier, L; Loew, D; Goyffon, M; Fehlbaum, P; Hoffmann, Jules A; van Dorsselaer, A; Bulet, Philippe Characterization of novel cysteine-rich antimicrobial peptides from scorpion blood Article de journal J. Biol. Chem., 271 (47), p. 29537–29544, 1996, ISSN: 0021-9258. Résumé | BibTeX | Étiquettes: Anti-Bacterial Agents, Chromatography, Cysteine, Electron, Hemolymph, Hemolysis, High Pressure Liquid, Mass Spectrometry, Microscopy, Peptides, Scorpions @article{ehret-sabatier_characterization_1996, title = {Characterization of novel cysteine-rich antimicrobial peptides from scorpion blood}, author = { L. Ehret-Sabatier and D. Loew and M. Goyffon and P. Fehlbaum and Jules A. Hoffmann and A. van Dorsselaer and Philippe Bulet}, issn = {0021-9258}, year = {1996}, date = {1996-11-01}, journal = {J. Biol. Chem.}, volume = {271}, number = {47}, pages = {29537--29544}, abstract = {We have isolated, from the hemolymph of unchallenged scorpions of the species Androctonus australis, three distinct antimicrobial peptides, which we have fully characterized by Edman degradation, electrospray ionization mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry. Two are novel molecules: (i) androctonin, a 25-residue peptide with two disulfide bridges, active against both bacteria (Gram-positive and Gram-negative) and fungi and showing marked sequence homology to tachyplesins and polyphemusins from horseshoe crabs; and (ii) buthinin, a 34-residue antibacterial (Gram-positive and Gram-negative) peptide with three disulfide bridges. The third peptide contains 37 residues and three disulfide bridges and clearly belongs to the family of anti-Gram-positive insect defensins. We have synthesized androctonin and explored its activity spectrum and mode of action.}, keywords = {Anti-Bacterial Agents, Chromatography, Cysteine, Electron, Hemolymph, Hemolysis, High Pressure Liquid, Mass Spectrometry, Microscopy, Peptides, Scorpions}, pubstate = {published}, tppubtype = {article} } We have isolated, from the hemolymph of unchallenged scorpions of the species Androctonus australis, three distinct antimicrobial peptides, which we have fully characterized by Edman degradation, electrospray ionization mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry. Two are novel molecules: (i) androctonin, a 25-residue peptide with two disulfide bridges, active against both bacteria (Gram-positive and Gram-negative) and fungi and showing marked sequence homology to tachyplesins and polyphemusins from horseshoe crabs; and (ii) buthinin, a 34-residue antibacterial (Gram-positive and Gram-negative) peptide with three disulfide bridges. The third peptide contains 37 residues and three disulfide bridges and clearly belongs to the family of anti-Gram-positive insect defensins. We have synthesized androctonin and explored its activity spectrum and mode of action. |
| 11. | Gross, I; Georgel, Philippe ; Kappler, Christine ; Reichhart, Jean-Marc ; Hoffmann, Jules A Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin Article de journal Nucleic Acids Res., 24 (7), p. 1238–1245, 1996, ISSN: 0305-1048. Résumé | BibTeX | Étiquettes: Antimicrobial Cationic Peptides, Base Sequence, DNA Primers, DNA-Binding Proteins, Gene Expression Regulation, Genetic, Insect Hormones, Insect Proteins, NF-kappa B, Nuclear Proteins, Peptides, Phosphoproteins, Transcription, Transcription Factors, Transcriptional Activation @article{gross_drosophila_1996, title = {Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin}, author = { I. Gross and Philippe Georgel and Christine Kappler and Jean-Marc Reichhart and Jules A. Hoffmann}, issn = {0305-1048}, year = {1996}, date = {1996-04-01}, journal = {Nucleic Acids Res.}, volume = {24}, number = {7}, pages = {1238--1245}, abstract = {In Drosophila, bacterial challenge induces the rapid transcription of several genes encoding potent antibacterial peptides. The upstream sequences of the diptericin and cecropin Al genes, which have been investigated in detail, contain two, respectively one sequence element homologous to the binding site of the mammalian nuclear factor kappaB. These elements have been shown to be mandatory for immune-induced transcription of both genes. Functional studies have shown that these kappaB-related elements can be the target for the Drosophila Rel proteins dorsal and Dif. Here we present a comparative analysis of the transactivating capacities of these proteins on reporter genes fused to either the diptericin or the cecropin kappaB-related motifs. We conclude from our results: (i) the kappaB motifs of the diptericin and cecropin genes are not functionally equivalent; (ii) the dorsal and Dif proteins have distinct DNA-binding characteristics; (iii) dorsal and Dif can heterodimerize in vitro; (iv) mutants containing no copies of dorsal and a single copy of Dif retain their full capacity to express the diptericin and cecropin genes in response to challenge.}, keywords = {Antimicrobial Cationic Peptides, Base Sequence, DNA Primers, DNA-Binding Proteins, Gene Expression Regulation, Genetic, Insect Hormones, Insect Proteins, NF-kappa B, Nuclear Proteins, Peptides, Phosphoproteins, Transcription, Transcription Factors, Transcriptional Activation}, pubstate = {published}, tppubtype = {article} } In Drosophila, bacterial challenge induces the rapid transcription of several genes encoding potent antibacterial peptides. The upstream sequences of the diptericin and cecropin Al genes, which have been investigated in detail, contain two, respectively one sequence element homologous to the binding site of the mammalian nuclear factor kappaB. These elements have been shown to be mandatory for immune-induced transcription of both genes. Functional studies have shown that these kappaB-related elements can be the target for the Drosophila Rel proteins dorsal and Dif. Here we present a comparative analysis of the transactivating capacities of these proteins on reporter genes fused to either the diptericin or the cecropin kappaB-related motifs. We conclude from our results: (i) the kappaB motifs of the diptericin and cecropin genes are not functionally equivalent; (ii) the dorsal and Dif proteins have distinct DNA-binding characteristics; (iii) dorsal and Dif can heterodimerize in vitro; (iv) mutants containing no copies of dorsal and a single copy of Dif retain their full capacity to express the diptericin and cecropin genes in response to challenge. |
| 10. | Fehlbaum, P; Bulet, Philippe; Chernysh, S; Briand, J P; Roussel, J P; Letellier, L; Hetru, Charles; Hoffmann, Jules A Structure-activity analysis of thanatin, a 21-residue inducible insect defense peptide with sequence homology to frog skin antimicrobial peptides Article de journal Proc. Natl. Acad. Sci. U.S.A., 93 (3), p. 1221–1225, 1996, ISSN: 0027-8424. Résumé | BibTeX | Étiquettes: Amino Acid, Amphibian Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Antimicrobial Cationic Peptides, Cyclic, Fungi, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemiptera, Mass Spectrometry, Microbial Sensitivity Tests, Peptides, Ranidae, Sequence Homology, Skin, Structure-Activity Relationship @article{fehlbaum_structure-activity_1996, title = {Structure-activity analysis of thanatin, a 21-residue inducible insect defense peptide with sequence homology to frog skin antimicrobial peptides}, author = { P. Fehlbaum and Philippe Bulet and S. Chernysh and J. P. Briand and J. P. Roussel and L. Letellier and Charles Hetru and Jules A. Hoffmann}, issn = {0027-8424}, year = {1996}, date = {1996-02-01}, journal = {Proc. Natl. Acad. Sci. U.S.A.}, volume = {93}, number = {3}, pages = {1221--1225}, abstract = {Immune challenge to the insect Podisus maculiventris induces synthesis of a 21-residue peptide with sequence homology to frog skin antimicrobial peptides of the brevinin family. The insect and frog peptides have in common a C-terminally located disulfide bridge delineating a cationic loop. The peptide is bactericidal and fungicidal, exhibiting the largest antimicrobial spectrum observed so far for an insect defense peptide. An all-D-enantiomer is nearly inactive against Gram-negative bacteria and some Gram-positive strains but is fully active against fungi and other Gram-positive bacteria, suggesting that more than one mechanism accounts for the antimicrobial activity of this peptide. Studies with truncated synthetic isoforms underline the role of the C-terminal loop and flanking residues for the activity of this molecule for which we propose the name thanatin.}, keywords = {Amino Acid, Amphibian Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Antimicrobial Cationic Peptides, Cyclic, Fungi, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemiptera, Mass Spectrometry, Microbial Sensitivity Tests, Peptides, Ranidae, Sequence Homology, Skin, Structure-Activity Relationship}, pubstate = {published}, tppubtype = {article} } Immune challenge to the insect Podisus maculiventris induces synthesis of a 21-residue peptide with sequence homology to frog skin antimicrobial peptides of the brevinin family. The insect and frog peptides have in common a C-terminally located disulfide bridge delineating a cationic loop. The peptide is bactericidal and fungicidal, exhibiting the largest antimicrobial spectrum observed so far for an insect defense peptide. An all-D-enantiomer is nearly inactive against Gram-negative bacteria and some Gram-positive strains but is fully active against fungi and other Gram-positive bacteria, suggesting that more than one mechanism accounts for the antimicrobial activity of this peptide. Studies with truncated synthetic isoforms underline the role of the C-terminal loop and flanking residues for the activity of this molecule for which we propose the name thanatin. |
| 9. | Hoffmann, Jules A; Reichhart, Jean-Marc ; Hetru, Charles Innate immunity in higher insects Article de journal Curr. Opin. Immunol., 8 (1), p. 8–13, 1996, ISSN: 0952-7915. Résumé | BibTeX | Étiquettes: Base Sequence, Cyclic, Immunity, Immunologic, Immunological, Innate, Insects, Models, Peptide Hydrolases, Peptides, Receptors @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 = {Base Sequence, Cyclic, Immunity, Immunologic, Immunological, Innate, Insects, Models, Peptide Hydrolases, Peptides, Receptors}, 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. |
1995 |
|
Articles de journaux |
|
| 8. | Lemaitre, Bruno; Kromer-Metzger, E; Michaut, Lydia ; Nicolas, E; Meister, Marie ; Georgel, Philippe ; Reichhart, Jean-Marc ; Hoffmann, Jules A A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense Article de journal Proc. Natl. Acad. Sci. U.S.A., 92 (21), p. 9465–9469, 1995, ISSN: 0027-8424. Résumé | BibTeX | Étiquettes: Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Bacterial Infections, Base Sequence, Gene Expression Regulation, Genes, Glycopeptides, Insect, Insect Hormones, Insect Proteins, Male, Mutation, Mycoses, Nucleic Acid, Peptides, Protein Binding, Recessive, Regulatory Sequences, Reporter, Survival Analysis @article{lemaitre_recessive_1995, title = {A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense}, author = { Bruno Lemaitre and E. Kromer-Metzger and Lydia Michaut and E. Nicolas and Marie Meister and Philippe Georgel and Jean-Marc Reichhart and Jules A. Hoffmann}, issn = {0027-8424}, year = {1995}, date = {1995-10-01}, journal = {Proc. Natl. Acad. Sci. U.S.A.}, volume = {92}, number = {21}, pages = {9465--9469}, abstract = {In this paper we report a recessive mutation, immune deficiency (imd), that impairs the inducibility of all genes encoding antibacterial peptides during the immune response of Drosophila. When challenged with bacteria, flies carrying this mutation show a lower survival rate than wild-type flies. We also report that, in contrast to the antibacterial peptides, the antifungal peptide drosomycin remains inducible in a homozygous imd mutant background. These results point to the existence of two different pathways leading to the expression of two types of target genes, encoding either the antibacterial peptides or the antifungal peptide drosomycin.}, keywords = {Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Bacterial Infections, Base Sequence, Gene Expression Regulation, Genes, Glycopeptides, Insect, Insect Hormones, Insect Proteins, Male, Mutation, Mycoses, Nucleic Acid, Peptides, Protein Binding, Recessive, Regulatory Sequences, Reporter, Survival Analysis}, pubstate = {published}, tppubtype = {article} } In this paper we report a recessive mutation, immune deficiency (imd), that impairs the inducibility of all genes encoding antibacterial peptides during the immune response of Drosophila. When challenged with bacteria, flies carrying this mutation show a lower survival rate than wild-type flies. We also report that, in contrast to the antibacterial peptides, the antifungal peptide drosomycin remains inducible in a homozygous imd mutant background. These results point to the existence of two different pathways leading to the expression of two types of target genes, encoding either the antibacterial peptides or the antifungal peptide drosomycin. |
| 7. | Levashina, Elena A; Ohresser, S; Bulet, Philippe ; Reichhart, Jean-Marc ; Hetru, Charles ; Hoffmann, Jules A Metchnikowin, a novel immune-inducible proline-rich peptide from Drosophila with antibacterial and antifungal properties Article de journal Eur. J. Biochem., 233 (2), p. 694–700, 1995, ISSN: 0014-2956. Résumé | BibTeX | Étiquettes: Anti-Bacterial Agents, Antifungal Agents, Antimicrobial Cationic Peptides, Bacteria, Base Sequence, Cells, Chromosome Mapping, Cloning, Cultured, Genetic, Molecular, Peptides, Proline, Transcription @article{levashina_metchnikowin_1995, title = {Metchnikowin, a novel immune-inducible proline-rich peptide from Drosophila with antibacterial and antifungal properties}, author = { Elena A. Levashina and S. Ohresser and Philippe Bulet and Jean-Marc Reichhart and Charles Hetru and Jules A. Hoffmann}, issn = {0014-2956}, year = {1995}, date = {1995-10-01}, journal = {Eur. J. Biochem.}, volume = {233}, number = {2}, pages = {694--700}, abstract = {One of the characteristics of the host defense of higher insects is the rapid and transient synthesis of a variety of potent antimicrobial peptides. To date, several distinct inducible antimicrobial peptides or peptide families have been totally or partially characterized. We present here the isolation and characterization of a novel 26-residue proline-rich immune-inducible peptide from Drosophila, which exhibits both antibacterial (Gram-positive) and antifungal activities. Peptide sequencing and cDNA cloning indicate the presense of two isoforms in our Drosophila Oregon strain, which differ by one residue (His compared to Arg) as a consequence of a single nucleotide change. The gene, which maps in position 52A1-2 on the right arm of the second chromosome, is expressed in the fat body after immune challenge. The novel peptide, which we propose to name metchnikowin, is a member of a family of proline-rich peptides, and we discuss the possible evolutionary relationships within this family.}, keywords = {Anti-Bacterial Agents, Antifungal Agents, Antimicrobial Cationic Peptides, Bacteria, Base Sequence, Cells, Chromosome Mapping, Cloning, Cultured, Genetic, Molecular, Peptides, Proline, Transcription}, pubstate = {published}, tppubtype = {article} } One of the characteristics of the host defense of higher insects is the rapid and transient synthesis of a variety of potent antimicrobial peptides. To date, several distinct inducible antimicrobial peptides or peptide families have been totally or partially characterized. We present here the isolation and characterization of a novel 26-residue proline-rich immune-inducible peptide from Drosophila, which exhibits both antibacterial (Gram-positive) and antifungal activities. Peptide sequencing and cDNA cloning indicate the presense of two isoforms in our Drosophila Oregon strain, which differ by one residue (His compared to Arg) as a consequence of a single nucleotide change. The gene, which maps in position 52A1-2 on the right arm of the second chromosome, is expressed in the fat body after immune challenge. The novel peptide, which we propose to name metchnikowin, is a member of a family of proline-rich peptides, and we discuss the possible evolutionary relationships within this family. |
| 6. | Hoffmann, Jules A Innate immunity of insects Article de journal Curr. Opin. Immunol., 7 (1), p. 4–10, 1995, ISSN: 0952-7915. Résumé | BibTeX | Étiquettes: Anti-Bacterial Agents, Blood Proteins, Cellular, Defensins, Gene Expression Regulation, Immunity, Innate, Insects, Peptides @article{hoffmann_innate_1995, title = {Innate immunity of insects}, author = { Jules A. Hoffmann}, issn = {0952-7915}, year = {1995}, date = {1995-02-01}, journal = {Curr. Opin. Immunol.}, volume = {7}, number = {1}, pages = {4--10}, abstract = {Insects are particularly resistant to microorganisms. Their host-defense system relies on several innate reactions: upon injury, the immediate onset of two proteolytic cascades leading to localized blood clotting and to melanization, the latter process involving production of cytotoxic molecules (namely reactive oxygen intermediates); the phagocytosis of bacteria and the encapsulation of larger parasites by blood cells; the induced synthesis by the fat body of a battery of potent antimicrobial peptides/polypeptides which are secreted into the hemolymph where they act synergistically to kill the invading microorganisms. The insect host defence system shares many of the basic characteristics of the mammalian acute phase response, especially at the level of the coordinate control of gene expression, where similar cis-regulatory and inducible transactivators appear to play key functions. The powerful techniques developed to study the genetics of Drosophila provide a unique opportunity to dissect the development and differentiation of this primordial immune system and may contribute to our understanding of the innate immune response in higher organisms.}, keywords = {Anti-Bacterial Agents, Blood Proteins, Cellular, Defensins, Gene Expression Regulation, Immunity, Innate, Insects, Peptides}, pubstate = {published}, tppubtype = {article} } Insects are particularly resistant to microorganisms. Their host-defense system relies on several innate reactions: upon injury, the immediate onset of two proteolytic cascades leading to localized blood clotting and to melanization, the latter process involving production of cytotoxic molecules (namely reactive oxygen intermediates); the phagocytosis of bacteria and the encapsulation of larger parasites by blood cells; the induced synthesis by the fat body of a battery of potent antimicrobial peptides/polypeptides which are secreted into the hemolymph where they act synergistically to kill the invading microorganisms. The insect host defence system shares many of the basic characteristics of the mammalian acute phase response, especially at the level of the coordinate control of gene expression, where similar cis-regulatory and inducible transactivators appear to play key functions. The powerful techniques developed to study the genetics of Drosophila provide a unique opportunity to dissect the development and differentiation of this primordial immune system and may contribute to our understanding of the innate immune response in higher organisms. |
1994 |
|
Articles de journaux |
|
| 5. | Fehlbaum, P; Bulet, Philippe; Michaut, L; Lagueux, Marie; Broekaert, W F; Hetru, Charles; Hoffmann, Jules A Insect immunity. Septic injury of Drosophila induces the synthesis of a potent antifungal peptide with sequence homology to plant antifungal peptides Article de journal J. Biol. Chem., 269 (52), p. 33159–33163, 1994, ISSN: 0021-9258. Résumé | BibTeX | Étiquettes: Amino Acid, Antifungal Agents, Base Sequence, Cloning, Complementary, DNA, Insect Proteins, Male, Messenger, Microbial Sensitivity Tests, Molecular, Peptide Biosynthesis, Peptides, Plants, Protein Biosynthesis, Protein Precursors, Proteins, RNA, Sequence Homology @article{fehlbaum_insect_1994, title = {Insect immunity. Septic injury of Drosophila induces the synthesis of a potent antifungal peptide with sequence homology to plant antifungal peptides}, author = {P. Fehlbaum and Philippe Bulet and L. Michaut and Marie Lagueux and W. F. Broekaert and Charles Hetru and Jules A. Hoffmann}, issn = {0021-9258}, year = {1994}, date = {1994-12-01}, journal = {J. Biol. Chem.}, volume = {269}, number = {52}, pages = {33159--33163}, abstract = {In response to a septic injury (pricking with a bacteria-soaked needle) larvae and adults of Drosophila produce considerable amounts of a 44-residue peptide containing 8 cysteines engaged in intramolecular disulfide bridges. The peptide is synthesized in the fat body, a functional homologue of the mammalian liver, and secreted into the blood of the insect. It exhibits potent antifungal activity but is inactive against bacteria. This novel inducible peptide, which we propose to name drosomycin, shows a significant homology with a family of 5-kDa cysteine-rich plant antifungal peptides recently isolated from seeds of Brassicaceae. This finding underlines that plants and insects can rely on similar molecules in their innate host defense.}, keywords = {Amino Acid, Antifungal Agents, Base Sequence, Cloning, Complementary, DNA, Insect Proteins, Male, Messenger, Microbial Sensitivity Tests, Molecular, Peptide Biosynthesis, Peptides, Plants, Protein Biosynthesis, Protein Precursors, Proteins, RNA, Sequence Homology}, pubstate = {published}, tppubtype = {article} } In response to a septic injury (pricking with a bacteria-soaked needle) larvae and adults of Drosophila produce considerable amounts of a 44-residue peptide containing 8 cysteines engaged in intramolecular disulfide bridges. The peptide is synthesized in the fat body, a functional homologue of the mammalian liver, and secreted into the blood of the insect. It exhibits potent antifungal activity but is inactive against bacteria. This novel inducible peptide, which we propose to name drosomycin, shows a significant homology with a family of 5-kDa cysteine-rich plant antifungal peptides recently isolated from seeds of Brassicaceae. This finding underlines that plants and insects can rely on similar molecules in their innate host defense. |
| 4. | Cociancich, S; Dupont, A; Hegy, G; Lanot, R; Holder, F; Hetru, Charles; Hoffmann, Jules A; Bulet, Philippe Novel inducible antibacterial peptides from a hemipteran insect, the sap-sucking bug Pyrrhocoris apterus Article de journal Biochem. J., 300 ( Pt 2) , p. 567–575, 1994, ISSN: 0264-6021. Résumé | BibTeX | Étiquettes: Amino Acid, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Blood Proteins, Chromatography, Defensins, Gas Chromatography-Mass Spectrometry, Gel, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemiptera, Hemolymph, Insect Proteins, Peptides, Sequence Homology @article{cociancich_novel_1994, title = {Novel inducible antibacterial peptides from a hemipteran insect, the sap-sucking bug Pyrrhocoris apterus}, author = { S. Cociancich and A. Dupont and G. Hegy and R. Lanot and F. Holder and Charles Hetru and Jules A. Hoffmann and Philippe Bulet}, issn = {0264-6021}, year = {1994}, date = {1994-06-01}, journal = {Biochem. J.}, volume = {300 ( Pt 2)}, pages = {567--575}, abstract = {Insects belonging to the recent orders of the endopterygote clade (Lepidoptera, Diptera, Hymenoptera and Coleoptera) respond to bacterial challenge by the rapid and transient synthesis of a battery of potent antibacterial peptides which are secreted into their haemolymph. Here we present the first report on inducible antibacterial molecules in the sap-sucking bug Pyrrhocoris apterus, a representative species of the Hemiptera, which predated the Endoptergotes by at least 50 million years in evolution. We have isolated and characterized from immune blood of this species three novel peptides or polypeptides: (i) a 43-residue cysteine-rich anti-(Gram-positive bacteria) peptide which is a new member of the family of insect defensins; (ii) a 20-residue proline-rich peptide carrying an O-glycosylated substitution (N-acetylgalactosamine), active against Gram-negative bacteria; (iii) a 133-residue glycine-rich polypeptide also active against Gram-negative bacteria. The proline-rich peptide shows high sequence similarities with drosocin, an O-glycosylated antibacterial peptide from Drosophila, and also with the N-terminal domain of diptericin, an inducible 9 kDa antibacterial peptide from members of the order Diptera, whereas the glycine-rich peptide has similarities with the glycine-rich domain of diptericin. We discuss the evolutionary aspects of these findings.}, keywords = {Amino Acid, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Blood Proteins, Chromatography, Defensins, Gas Chromatography-Mass Spectrometry, Gel, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemiptera, Hemolymph, Insect Proteins, Peptides, Sequence Homology}, pubstate = {published}, tppubtype = {article} } Insects belonging to the recent orders of the endopterygote clade (Lepidoptera, Diptera, Hymenoptera and Coleoptera) respond to bacterial challenge by the rapid and transient synthesis of a battery of potent antibacterial peptides which are secreted into their haemolymph. Here we present the first report on inducible antibacterial molecules in the sap-sucking bug Pyrrhocoris apterus, a representative species of the Hemiptera, which predated the Endoptergotes by at least 50 million years in evolution. We have isolated and characterized from immune blood of this species three novel peptides or polypeptides: (i) a 43-residue cysteine-rich anti-(Gram-positive bacteria) peptide which is a new member of the family of insect defensins; (ii) a 20-residue proline-rich peptide carrying an O-glycosylated substitution (N-acetylgalactosamine), active against Gram-negative bacteria; (iii) a 133-residue glycine-rich polypeptide also active against Gram-negative bacteria. The proline-rich peptide shows high sequence similarities with drosocin, an O-glycosylated antibacterial peptide from Drosophila, and also with the N-terminal domain of diptericin, an inducible 9 kDa antibacterial peptide from members of the order Diptera, whereas the glycine-rich peptide has similarities with the glycine-rich domain of diptericin. We discuss the evolutionary aspects of these findings. |
1992 |
|
Articles de journaux |
|
| 3. | Bulet, Philippe; Cociancich, S; Reuland, M; Sauber, F; Bischoff, R; Hegy, G; Dorsselaer, Van A; Hetru, Charles; Hoffmann, Jules A A novel insect defensin mediates the inducible antibacterial activity in larvae of the dragonfly Aeschna cyanea (Paleoptera, Odonata) Article de journal Eur. J. Biochem., 209 (3), p. 977–984, 1992, ISSN: 0014-2956. Résumé | BibTeX | Étiquettes: Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Blood Bactericidal Activity, Blood Proteins, Defensins, Hemolymph, Insect Proteins, Insects, Larva, Mass Spectrometry, Peptides @article{bulet_novel_1992, title = {A novel insect defensin mediates the inducible antibacterial activity in larvae of the dragonfly Aeschna cyanea (Paleoptera, Odonata)}, author = { Philippe Bulet and S. Cociancich and M. Reuland and F. Sauber and R. Bischoff and G. Hegy and A. Van Dorsselaer and Charles Hetru and Jules A. Hoffmann}, issn = {0014-2956}, year = {1992}, date = {1992-11-01}, journal = {Eur. J. Biochem.}, volume = {209}, number = {3}, pages = {977--984}, abstract = {The injection of low doses of bacteria into the aquatic larvae of dragonflies (Aeschna cyanea, Odonata, Paleoptera) induces the appearance in their hemolymph of a potent antibacterial activity. We have isolated a 38-residue peptide from this hemolymph which is strongly active against Gram-positive bacteria and also shows activity against one of the Gram-negative bacteria which was tested. The peptide is a novel member of the insect defensin family of inducible antibacterial peptides, which had so far only been reported from the higher insect orders believed to have evolved 100 million years after the Paleoptera. Aeschna defensin is more potent than defensin from the dipteran Phormia, from which its structure differs in several interesting aspects, which are discussed in the paper.}, keywords = {Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Blood Bactericidal Activity, Blood Proteins, Defensins, Hemolymph, Insect Proteins, Insects, Larva, Mass Spectrometry, Peptides}, pubstate = {published}, tppubtype = {article} } The injection of low doses of bacteria into the aquatic larvae of dragonflies (Aeschna cyanea, Odonata, Paleoptera) induces the appearance in their hemolymph of a potent antibacterial activity. We have isolated a 38-residue peptide from this hemolymph which is strongly active against Gram-positive bacteria and also shows activity against one of the Gram-negative bacteria which was tested. The peptide is a novel member of the insect defensin family of inducible antibacterial peptides, which had so far only been reported from the higher insect orders believed to have evolved 100 million years after the Paleoptera. Aeschna defensin is more potent than defensin from the dipteran Phormia, from which its structure differs in several interesting aspects, which are discussed in the paper. |
| 2. | Hoffmann, Jules A; Hetru, Charles Insect defensins: inducible antibacterial peptides Article de journal Immunol. Today, 13 (10), p. 411–415, 1992, ISSN: 0167-5699. Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Bacterial Infections, Blood Bactericidal Activity, Blood Proteins, Defensins, Insects, Peptides, Sequence Homology @article{hoffmann_insect_1992, title = {Insect defensins: inducible antibacterial peptides}, author = { Jules A. Hoffmann and Charles Hetru}, doi = {10.1016/0167-5699(92)90092-L}, issn = {0167-5699}, year = {1992}, date = {1992-10-01}, journal = {Immunol. Today}, volume = {13}, number = {10}, pages = {411--415}, abstract = {In response to bacterial challenge or trauma, insects produce a battery of bactericidal or bacteriostatic molecules with a broad spectrum of activity against Gram-positive and/or Gram-negative bacteria; most are small-sized cationic peptides. This review focuses on insect defensins, a large group of inducible antibacterial peptides that are present both in ancient and recent insect orders. This immune response of insects shares many of the characteristics of the mammalian acute phase response.}, keywords = {Amino Acid, Bacterial Infections, Blood Bactericidal Activity, Blood Proteins, Defensins, Insects, Peptides, Sequence Homology}, pubstate = {published}, tppubtype = {article} } In response to bacterial challenge or trauma, insects produce a battery of bactericidal or bacteriostatic molecules with a broad spectrum of activity against Gram-positive and/or Gram-negative bacteria; most are small-sized cationic peptides. This review focuses on insect defensins, a large group of inducible antibacterial peptides that are present both in ancient and recent insect orders. This immune response of insects shares many of the characteristics of the mammalian acute phase response. |
1987 |
|
Articles de journaux |
|
| 1. | Debono, M; Barnhart, M; Carrell, C B; Hoffmann, Jules A; Occolowitz, J L; Abbott, B J; Fukuda, D S; Hamill, R L; Biemann, K; Herlihy, W C A21978C, a complex of new acidic peptide antibiotics: isolation, chemistry, and mass spectral structure elucidation Article de journal J. Antibiot., 40 (6), p. 761–777, 1987, ISSN: 0021-8820. Résumé | BibTeX | Étiquettes: Acylation, Amino Acids, Anti-Bacterial Agents, Chemical Phenomena, Chemistry, Chromatography, Cyclic, Fatty Acids, Gas Chromatography-Mass Spectrometry, High Pressure Liquid, Hydrolysis, Magnetic Resonance Spectroscopy, Mass Spectrometry, Molecular Conformation, Peptides, Spectrophotometry, Streptomyces @article{debono_a21978c_1987, title = {A21978C, a complex of new acidic peptide antibiotics: isolation, chemistry, and mass spectral structure elucidation}, author = { M. Debono and M. Barnhart and C. B. Carrell and Jules A. Hoffmann and J. L. Occolowitz and B. J. Abbott and D. S. Fukuda and R. L. Hamill and K. Biemann and W. C. Herlihy}, issn = {0021-8820}, year = {1987}, date = {1987-01-01}, journal = {J. Antibiot.}, volume = {40}, number = {6}, pages = {761--777}, abstract = {A21978C, produced by Streptomyces roseosporus, NRRL 11379, is a complex of new acidic lipopeptolide antibiotics which inhibits Gram-positive bacteria. HPLC separation of the various components from the purified complex resulted in the isolation of A21978C1, -C2 and -C3 (major components) and -C4, -C5, and -C0 (minor components). Each of these components was fermented with cultures of Actinoplanes utahensis (NRRL 12052) to give the identical inactive peptide ("A21978C nucleus") by removal of the fatty acid acyl groups from the N-terminus. This peptide was composed of 13 amino acids: L-kynurenine, L-threo-3-methylglutamic acid, L-asparagine, L-aspartic acid (3 residues), glycine (2 residues), L-tryptophan, L-ornithine, D-alanine, D-serine and L-threonine. The amino acid sequence was determined using a combination of the Edman degradation and gas chromatography mass spectrum (GC-MS) analysis of appropriately derivatized peptides obtained from partial hydrolysis. Each major component was shown to be acylated with a branched chain fatty acid at the N-terminus and the structure of this fatty acid was determined by 1H NMR and mass spectral methods. A structure for A21978C was assigned on the basis of this degradative and physico-chemical information.}, keywords = {Acylation, Amino Acids, Anti-Bacterial Agents, Chemical Phenomena, Chemistry, Chromatography, Cyclic, Fatty Acids, Gas Chromatography-Mass Spectrometry, High Pressure Liquid, Hydrolysis, Magnetic Resonance Spectroscopy, Mass Spectrometry, Molecular Conformation, Peptides, Spectrophotometry, Streptomyces}, pubstate = {published}, tppubtype = {article} } A21978C, produced by Streptomyces roseosporus, NRRL 11379, is a complex of new acidic lipopeptolide antibiotics which inhibits Gram-positive bacteria. HPLC separation of the various components from the purified complex resulted in the isolation of A21978C1, -C2 and -C3 (major components) and -C4, -C5, and -C0 (minor components). Each of these components was fermented with cultures of Actinoplanes utahensis (NRRL 12052) to give the identical inactive peptide ("A21978C nucleus") by removal of the fatty acid acyl groups from the N-terminus. This peptide was composed of 13 amino acids: L-kynurenine, L-threo-3-methylglutamic acid, L-asparagine, L-aspartic acid (3 residues), glycine (2 residues), L-tryptophan, L-ornithine, D-alanine, D-serine and L-threonine. The amino acid sequence was determined using a combination of the Edman degradation and gas chromatography mass spectrum (GC-MS) analysis of appropriately derivatized peptides obtained from partial hydrolysis. Each major component was shown to be acylated with a branched chain fatty acid at the N-terminus and the structure of this fatty acid was determined by 1H NMR and mass spectral methods. A structure for A21978C was assigned on the basis of this degradative and physico-chemical information. |
Partenaires:
Informations générales
Dernières actualités
Adresse
IBMC - UPR9022 CNRS
15 rue René Descartes
67084 STRASBOURG cedex
Tel: (33) 03 88 41 70 37
Fax: (33) 03 88 60 69 22
15 rue René Descartes
67084 STRASBOURG cedex
Tel: (33) 03 88 41 70 37
Fax: (33) 03 88 60 69 22
© M3I – UPR9022 CNRS