RNA interference and receptors

@article{Martins_2019jbio,

title = {Les insectes : un fantastique réservoir de virus et de gènes antiviraux},

author = {NE Martins and RP Olmo and ERGR Aguiar and JT Marques and JL Imler},

url = {https://www.biologie-journal.org/articles/jbio/abs/2018/02/jbio190008/jbio190008.html},

doi = {10.1051/jbio/2019008},

year  = {2019},

date = {2019-04-11},

journal = {Biologie Aujourd'hui},

volume = {212},

number = {3-4},

pages = {101-106},

abstract = {Les insectes forment le groupe d’animaux qui présente la plus grande diversité. Des travaux récents de métagénomique montrent qu’ils peuvent être infectés par une diversité extraordinaire de virus. Parmi eux, les arbovirus (arthropod-borne viruses) peuvent être transmis à l’Homme par les insectes hématophages, notamment les moustiques. Le séquençage à haut débit des petits ARN des insectes fournit des informations sur leur virome, un paramètre qui pourrait contribuer à expliquer la dynamique de la transmission des maladies infectieuses par des insectes vecteurs. D’autre part, la caractérisation des mécanismes qui restreignent les infections virales chez les insectes révèle des innovations génétiques qui pourraient à terme inspirer de nouvelles stratégies antivirales.},

keywords = {antiviral immunity, ARN interference, imler, Insect, M3i, Marques, metagenomic, virome},

pubstate = {published},

tppubtype = {article}

}

@article{veillard_drosophila_2015,

title = {Drosophila melanogaster clip-domain serine proteases: Structure, function and regulation},

author = {Florian Veillard and Laurent Troxler and Jean-Marc Reichhart},

url = {http://www.sciencedirect.com/science/article/pii/S030090841500317X},

doi = {10.1016/j.biochi.2015.10.007},

isbn = {0300-9084},

year  = {2015},

date = {2015-10-08},

journal = {Biochimie},

volume = {122},

pages = {255-269},

abstract = {Mammalian chymotrypsin-like serine proteases (SPs) are one of the best-studied family of enzymes with roles in a wide range of physiological processes, including digestion, blood coagulation, fibrinolysis and humoral immunity. Extracellular SPs can form cascades, in which one protease activates the zymogen of the next protease in the chain, to amplify physiological or pathological signals. These extracellular SPs are generally multi-domain proteins, with pro-domains that are involved in protein–protein interactions critical for the sequential organization of the cascades, the control of their intensity and their proper localization. Far less is known about invertebrate SPs than their mammalian counterparts. In insect genomes, SPs and their proteolytically inactive homologs (SPHs) constitute large protein families. In addition to the chymotrypsin fold, many of these proteins contain additional structural domains, often with conserved mammalian orthologues. However, the largest group of arthropod SP regulatory modules is the clip domains family, which has only been identified in arthropods. The clip-domain SPs are extracellular and have roles in the immune response and embryonic development. The powerful reverse-genetics tools in Drosophila melanogaster have been essential to identify the functions of clip-SPs and their organization in sequential cascades. This review focuses on the current knowledge of Drosophila clip-SPs and presents, when necessary, data obtained in other insect models. We will first cover the biochemical and structural features of clip domain SPs and SPHs. Clip-SPs are implicated in three main biological processes: the control of the dorso-ventral patterning during embryonic development; the activation of the Toll-mediated response to microbial infections and the prophenoloxydase cascade, which triggers melanization. Finally, we review the regulation of SPs and SPHs, from specificity of activation to inhibition by endogenous or pathogen-encoded inhibitors.},

keywords = {bioinformatic, Chymotrypsin, clip domain, Immunity, Insect, M3i, Melanization, reichhart, Serine Proteases, Serpin, Toll},

pubstate = {published},

tppubtype = {article}

}

@article{fukuyama_landscape_2013,

title = {Landscape of protein-protein interactions in Drosophila immune deficiency signaling during bacterial challenge},

author = {Hidehiro Fukuyama and Yann Verdier and Yongsheng Guan and Chieko Makino-Okamura and Victoria Shilova and Xi Liu and Elie Maksoud and Jun Matsubayashi and Iman Haddad and Kerstin Spirohn and Kenichiro Ono and Charles Hetru and Jean Rossier and Trey Ideker and Michael Boutros and Joëlle Vinh and Jules A Hoffmann},

doi = {10.1073/pnas.1304380110},

issn = {1091-6490},

year  = {2013},

date = {2013-06-01},

journal = {Proc. Natl. Acad. Sci. U.S.A.},

volume = {110},

number = {26},

pages = {10717--10722},

abstract = {The Drosophila defense against pathogens largely relies on the activation of two signaling pathways: immune deficiency (IMD) and Toll. The IMD pathway is triggered mainly by Gram-negative bacteria, whereas the Toll pathway responds predominantly to Gram-positive bacteria and fungi. The activation of these pathways leads to the rapid induction of numerous NF-κB-induced immune response genes, including antimicrobial peptide genes. The IMD pathway shows significant similarities with the TNF receptor pathway. Recent evidence indicates that the IMD pathway is also activated in response to various noninfectious stimuli (i.e., inflammatory-like reactions). To gain a better understanding of the molecular machinery underlying the pleiotropic functions of this pathway, we first performed a comprehensive proteomics analysis to identify the proteins interacting with the 11 canonical members of the pathway initially identified by genetic studies. We identified 369 interacting proteins (corresponding to 291 genes) in heat-killed Escherichia coli-stimulated Drosophila S2 cells, 92% of which have human orthologs. A comparative analysis of gene ontology from fly or human gene annotation databases points to four significant common categories: (i) the NuA4, nucleosome acetyltransferase of H4, histone acetyltransferase complex, (ii) the switching defective/sucrose nonfermenting-type chromatin remodeling complex, (iii) transcription coactivator activity, and (iv) translation factor activity. Here we demonstrate that sumoylation of the IκB kinase homolog immune response-deficient 5 plays an important role in the induction of antimicrobial peptide genes through a highly conserved sumoylation consensus site during bacterial challenge. Taken together, the proteomics data presented here provide a unique avenue for a comparative functional analysis of proteins involved in innate immune reactions in flies and mammals.},

keywords = {Amino Acid, Animals, Chromatin Assembly and Disassembly, Escherichia coli, functional proteomics, Genes, Genetically Modified, Histone Acetyltransferases, hoffmann, Host-Pathogen Interactions, Humans, IMD interactome, Insect, M3i, Models, Molecular, Protein Interaction Maps, Sequence Homology, Signal Transduction, small ubiquitin-like modifier},

pubstate = {published},

tppubtype = {article}

}

@article{limmer_pseudomonas_2011b,

title = {Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model},

author = {Stefanie Limmer and Samantha Haller and Eliana Drenkard and Janice Lee and Shen Yu and Christine Kocks and Frederick M Ausubel and Dominique Ferrandon},

doi = {10.1073/pnas.1114907108},

issn = {1091-6490},

year  = {2011},

date = {2011-10-01},

journal = {Proc. Natl. Acad. Sci. U.S.A.},

volume = {108},

number = {42},

pages = {17378--17383},

abstract = {An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host-pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated.},

keywords = {Animal, Animals, Bacteremia, Bacterial Proteins, Cellular, Disease Models, ferrandon, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, M3i, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{cronin_genome-wide_2009b,

title = {Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection},

author = {Shane J F Cronin and Nadine T Nehme and Stefanie Limmer and Samuel Liegeois and Andrew J Pospisilik and Daniel Schramek and Andreas Leibbrandt and Ricardo Matos de Simoes and Susanne Gruber and Urszula Puc and Ingo Ebersberger and Tamara Zoranovic and Gregory G Neely and Arndt von Haeseler and Dominique Ferrandon and Josef M Penninger},

doi = {10.1126/science.1173164},

issn = {1095-9203},

year  = {2009},

date = {2009-01-01},

journal = {Science},

volume = {325},

number = {5938},

pages = {340--343},

abstract = {Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We first employed whole-organism gene suppression, followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Therefore, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity.},

keywords = {*Genome, *RNA Interference, Animal, Animals, Cell Proliferation, Drosophila melanogaster/*genetics/immunology/*microbiology, Drosophila Proteins/genetics/metabolism, Epithelial Cells, Epithelial Cells/cytology/physiology, ferrandon, Genetically Modified, Genome, Hemocytes, Hemocytes/immunology/metabolism/microbiology, Homeostasis, Immunity, Innate, Innate/*genetics, Insect, Intestinal Mucosa, Intestinal Mucosa/cytology/immunology/metabolism/microbiology, Janus Kinases, Janus Kinases/genetics/metabolism, M3i, Models, RNA Interference, Serratia Infections, Serratia Infections/genetics/*immunology/microbiology, Serratia marcescens, Serratia marcescens/*immunology/physiology, Signal Transduction, STAT Transcription Factors, STAT Transcription Factors/genetics/metabolism, Stem Cells, Stem Cells/cytology/physiology},

pubstate = {published},

tppubtype = {article}

}

@article{frolet_boosting_2006,

title = {Boosting NF-kappaB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei},

author = {Cécile Frolet and Martine Thoma and Stéphanie A Blandin and Jules A Hoffmann and Elena A Levashina},

url = {http://www.ncbi.nlm.nih.gov/pubmed/17045818},

doi = {10.1016/j.immuni.2006.08.019},

issn = {1074-7613},

year  = {2006},

date = {2006-10-01},

journal = {Immunity},

volume = {25},

number = {4},

pages = {677--685},

abstract = {Anopheles gambiae, the major vector for the protozoan malaria parasite Plasmodium falciparum, mounts powerful antiparasitic responses that cause marked parasite loss during midgut invasion. Here, we showed that these antiparasitic defenses were composed of pre- and postinvasion phases and that the preinvasion phase was predominantly regulated by Rel1 and Rel2 members of the NF-kappaB transcription factors. Concurrent silencing of Rel1 and Rel2 decreased the basal expression of the major antiparasitic genes TEP1 and LRIM1 and abolished resistance of Anopheles to the rodent malaria parasite P. berghei. Conversely, depletion of a negative regulator of Rel1, Cactus, prior to infection, enhanced the basal expression of TEP1 and of other immune factors and completely prevented parasite development. Our findings uncover the crucial role of the preinvasion defense in the elimination of parasites, which is at least in part based on circulating blood molecules.},

keywords = {Animals, Anopheles gambiae, blandin, Gene Expression, Gene Expression Regulation, Genes, hoffmann, Immunity, Insect, M3i, NF-kappa B, Plasmodium berghei, telomerase},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{kocks_eater_2005,

title = {Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila},

author = {Christine Kocks and Ju Hyun Cho and Nadine Nehme and Johanna Ulvila and Alan M Pearson and Marie Meister and Charles Strom and Stephanie L Conto and Charles Hetru and Lynda M Stuart and Thilo Stehle and Jules A Hoffmann and Jean-Marc Reichhart and Dominique Ferrandon and Mika Rämet and Alan R B Ezekowitz},

doi = {10.1016/j.cell.2005.08.034},

issn = {0092-8674},

year  = {2005},

date = {2005-10-01},

journal = {Cell},

volume = {123},

number = {2},

pages = {335--346},

abstract = {Phagocytosis is a complex, evolutionarily conserved process that plays a central role in host defense against infection. We have identified a predicted transmembrane protein, Eater, which is involved in phagocytosis in Drosophila. Transcriptional silencing of the eater gene in a macrophage cell line led to a significant reduction in the binding and internalization of bacteria. Moreover, the N terminus of the Eater protein mediated direct microbial binding which could be inhibited with scavenger receptor ligands, acetylated, and oxidized low-density lipoprotein. In vivo, eater expression was restricted to blood cells. Flies lacking the eater gene displayed normal responses in NF-kappaB-like Toll and IMD signaling pathways but showed impaired phagocytosis and decreased survival after bacterial infection. Our results suggest that Eater is a major phagocytic receptor for a broad range of bacterial pathogens in Drosophila and provide a powerful model to address the role of phagocytosis in vivo.},

keywords = {Amino Acid, Amino Acid Motifs, Animals, Bacterial Infections, Cell Surface, Embryo, Escherichia coli, ferrandon, Flow Cytometry, Frameshift Mutation, Genes, Histidine, hoffmann, In Situ Hybridization, Insect, Insect Proteins, M3i, Macrophages, Membrane Proteins, messenger, Nonmammalian, Open Reading Frames, Phagocytosis, Receptors, reichhart, RNA, RNA Interference, Sequence Homology, Serratia marcescens},

pubstate = {published},

tppubtype = {article}

}

@article{fauny_drosophila_2005,

title = {Drosophila Lipid Storage Droplet 2 gene (Lsd-2) is expressed and controls lipid storage in wing imaginal discs},

author = {Jean Daniel Fauny and Joël Silber and Alain Zider},

url = {http://www.ncbi.nlm.nih.gov/pubmed/15704138},

doi = {10.1002/dvdy.20277},

issn = {1058-8388},

year  = {2005},

date = {2005-03-01},

urldate = {2011-10-24},

journal = {Developmental Dynamics: An Official Publication of the American Association of Anatomists},

volume = {232},

number = {3},

pages = {725--732},

abstract = {Lipid droplets are the major neutral lipid storage organelles in higher eukaryotes. The PAT domain proteins (Perilipin, ADRP [adipose differentiation related protein], and TIP47 [tail-interacting 47-kDa protein]) are associated with these structures. Perilipin and ADRP are involved in the regulation of lipid storage and metabolism in mammals. Two genes encoding PAT proteins, Drosophila Lipid Storage Droplet 2 Gene (Lsd-2) and Lsd-2, have been identified in Drosophila. Lsd-2 is expressed in fat bodies and in the female germ line and is involved in lipid storage in these tissues. We showed that Lsd-2 is expressed in third-instar wing imaginal discs in Drosophila, with higher levels in the wing pouch, which corresponds to the presumptive wing region of the wing disc. This specific expression pattern is correlated with a high level of neutral lipid accumulation. We also showed that neutral lipid deposition in the wing disc is severely reduced in an Lsd-2 mutant and is increased with Lsd-2 overexpression. Finally, we showed that overexpression of the vestigial (vg) pro-wing gene induces Lsd-2 expression, suggesting that Lsd-2 mediates a vg role during wing formation. Our results suggest that Lsd-2 function is not restricted to tissues directly involved in lipid storage and could play additional roles during development.},

keywords = {Animals, Biological, Drosophila, Drosophila Proteins, Embryo, Fat Body, Genes, I2CT, Imagerie, Insect, Larva, Lipid Metabolism, Metamorphosis, Mutation, Nonmammalian, Nuclear Proteins, Phosphoproteins, Wing},

pubstate = {published},

tppubtype = {article}

}

@article{imler_antimicrobial_2005,

title = {Antimicrobial peptides in Drosophila: structures, activities and gene regulation},

author = {Jean-Luc Imler and Philippe Bulet},

doi = {10.1159/000086648},

issn = {1660-2242},

year  = {2005},

date = {2005-01-01},

journal = {Chemical Immunology and Allergy},

volume = {86},

pages = {1--21},

abstract = {The production of antimicrobial peptides (AMPs) is an important aspect of host-defence in multicellular organisms. Biochemical analysis of the hemolymph of the fruit-fly Drosophila melanogaster and other Diptera has led to the discovery of eight classes of AMPs. These peptides can be grouped into three families based on their main biological targets, gram-positive bacteria (defensin), gram-negative bacteria (cecropins, drosocin, attacins, diptericin, MPAC), or fungi (drosomycin, metchnikowin). Drosophila AMPs are synthesized by the fat body in response to infection, and secreted into the blood. Most of them can also be induced in surface epithelia in a tissue-specific manner. Finally, some of them are constitutively expressed in defined tissues, such as the salivary glands or the reproductive tract. We review here the structures and activities of these AMPs, as well as the signalling cascades, which lead to their induction upon detection of infectious non-self.},

keywords = {Animals, Antimicrobial Cationic Peptides, Defensins, Gene Expression Regulation, Genes, Glycopeptides, imler, Immunity, Innate, Insect, Insect Proteins, M3i, Molecular Structure, Signal Transduction},

pubstate = {published},

tppubtype = {article}

}

@article{blandin_mosquito_2004,

title = {Mosquito immune responses against malaria parasites},

author = {Stéphanie A Blandin and Elena A Levashina},

issn = {0952-7915},

year  = {2004},

date = {2004-01-01},

journal = {Curr. Opin. Immunol.},

volume = {16},

number = {1},

pages = {16--20},

abstract = {Anopheline mosquitoes are the major vectors of human malaria. Mosquito-parasite interactions are a critical aspect of disease transmission and a potential target for malaria control. Mosquitoes vary in their innate ability to support development of the malaria parasite, but the molecular mechanisms that determine vector competence are poorly understood. This area of research has been revolutionized by recent advances in the mosquito genome characterization and by the development of new tools for functional gene analysis.},

keywords = {Animals, Anopheles, blandin, Gene Library, Genes, Hemocytes, Host-Parasite Interactions, Immunity, Innate, Insect, Insect Vectors, M3i, Malaria, Plasmodium},

pubstate = {published},

tppubtype = {article}

}

@article{gobert_dual_2003,

title = {Dual activation of the Drosophila toll pathway by two pattern recognition receptors},

author = {Vanessa Gobert and Marie Gottar and Alexey A Matskevich and Sophie Rutschmann and Julien Royet and Marcia Belvin and Jules A Hoffmann and Dominique Ferrandon},

doi = {10.1126/science.1085432},

issn = {1095-9203},

year  = {2003},

date = {2003-12-01},

journal = {Science},

volume = {302},

number = {5653},

pages = {2126--2130},

abstract = {The Toll-dependent defense against Gram-positive bacterial infections in Drosophila is mediated through the peptidoglycan recognition protein SA (PGRP-SA). A mutation termed osiris disrupts the Gram-negative binding protein 1 (GNBP1) gene and leads to compromised survival of mutant flies after Gram-positive infections, but not after fungal or Gram-negative bacterial challenge. Our results demonstrate that GNBP1 and PGRP-SA can jointly activate the Toll pathway. The potential for a combination of distinct proteins to mediate detection of infectious nonself in the fly will refine the concept of pattern recognition in insects.},

keywords = {Animals, Carrier Proteins, Cell Surface, DNA Transposable Elements, ferrandon, Gene Expression, Genes, Gram-Negative Bacteria, Gram-Positive Bacteria, Hemolymph, hoffmann, Hypocreales, Insect, Insect Proteins, M3i, Mutation, Phenotype, Receptors, Serine Endopeptidases, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{ligoxygakis_activation_2002,

title = {Activation of Drosophila Toll during fungal infection by a blood serine protease},

author = {Petros Ligoxygakis and Nadège Pelte and Jules A Hoffmann and Jean-Marc Reichhart},

doi = {10.1126/science.1072391},

issn = {1095-9203},

year  = {2002},

date = {2002-07-01},

journal = {Science},

volume = {297},

number = {5578},

pages = {114--116},

abstract = {Drosophila host defense to fungal and Gram-positive bacterial infection is mediated by the Spaetzle/Toll/cactus gene cassette. It has been proposed that Toll does not function as a pattern recognition receptor per se but is activated through a cleaved form of the cytokine Spaetzle. The upstream events linking infection to the cleavage of Spaetzle have long remained elusive. Here we report the identification of a central component of the fungal activation of Toll. We show that ethylmethane sulfonate-induced mutations in the persephone gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection.},

keywords = {Animals, Cell Surface, Chromosome Mapping, Escherichia coli, Female, Gene Expression Regulation, Genes, Gram-Positive Cocci, Hemolymph, hoffmann, Hypocreales, Insect, Insect Proteins, M3i, Male, Mutation, Protein Sorting Signals, Protein Structure, Receptors, reichhart, Serine Endopeptidases, Tertiary, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{ligoxygakis_critical_2002,

title = {Critical evaluation of the role of the Toll-like receptor 18-Wheeler in the host defense of Drosophila},

author = {Petros Ligoxygakis and Philippe Bulet and Jean-Marc Reichhart},

doi = {10.1093/embo-reports/kvf130},

issn = {1469-221X},

year  = {2002},

date = {2002-01-01},

journal = {EMBO Rep.},

volume = {3},

number = {7},

pages = {666--673},

abstract = {Essential aspects of innate immune responses to microbial infections appear to be conserved between insects and mammals. In particular, in both groups, transmembrane receptors of the Toll superfamily play a crucial role in activating immune defenses. The Drosophila Toll family member 18-Wheeler had been proposed to sense Gram-negative infection and direct selective expression of peptides active against Gram-negative bacteria. Here we re-examine the role of 18-Wheeler and show that in adults it is dispensable for immune responses. In larvae, 18wheeler is required for normal fat body development, and in mutant larvae induction of all antimicrobial peptide genes, and not only of those directed against Gram-negative bacteria, is compromised. 18-Wheeler does not qualify as a pattern recognition receptor of Gram-negative bacteria.},

keywords = {Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Cell Adhesion Molecules, Fat Body, Gene Expression Regulation, Genes, Immunohistochemistry, Immunologic, Insect, Insect Proteins, Larva, M3i, Mass, Matrix-Assisted Laser Desorption-Ionization, Membrane Proteins, Receptors, reichhart, Reporter, Spectrometry, Transgenes},

pubstate = {published},

tppubtype = {article}

}