I2CT

@article{Goto2021,

title = {Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila},

author = {Pragya Prakash and Arghyashree Roychowdhury-Sinha and Akira Goto},

url = {https://www.nature.com/articles/s41598-021-94973-0},

doi = {10.1038/s41598-021-94973-0},

year  = {2021},

date = {2021-07-30},

journal = {Scientific Reports},

volume = {11},

number = {15549},

abstract = {Drosophila immune deficiency (IMD) pathway is similar to the human tumor necrosis factor receptor (TNFR) signaling pathway and is preferentially activated by Gram-negative bacterial infection. Recent studies highlighted the importance of IMD pathway regulation as it is tightly controlled by numbers of negative regulators at multiple levels. Here, we report a new negative regulator of the IMD pathway, Verloren (Velo). Silencing of Velo led to constitutive expression of the IMD pathway dependent antimicrobial peptides (AMPs), and Escherichia coli stimulation further enhanced the AMP expression. Epistatic analysis indicated that Velo knock-down mediated AMP upregulation is dependent on the canonical members of the IMD pathway. The immune fluorescent study using overexpression constructs revealed that Velo resides both in the nucleus and cytoplasm, but the majority (~ 75%) is localized in the nucleus. We also observed from in vivo analysis that Velo knock-down flies exhibit significant upregulation of the AMP expression and reduced bacterial load. Survival experiments showed that Velo knock-down flies have a short lifespan and are susceptible to the infection of pathogenic Gram-negative bacteria, P. aeruginosa. Taken together, these data suggest that Velo is an additional new negative regulator of the IMD pathway, possibly acting in both the nucleus and cytoplasm.},

keywords = {bacteria, Biochemistry, DNA, Fungi, Gene Expression, gene regulation, Genetics, hoffmann, Immunochemistry, Immunology, infection, inflammation, Innate immune cells, innate immunity, M3i, microbiology, Molecular Biology, pathogens, RNA, RNAi, Signal Transduction, Transcription},

pubstate = {published},

tppubtype = {article}

}

@article{frechin_expression_2014,

title = {Expression of nuclear and mitochondrial genes encoding ATP synthase is synchronized by disassembly of a multisynthetase complex.},

author = {Mathieu Frechin and Ludovic Enkler and Emmanuel Tetaud and Daphné Laporte and Bruno Senger and Corinne Blancard and Philippe Hammann and Gaétan Bader and Sandra Clauder-Münster and Lars M Steinmetz and Robert Pierre Martin and Jean-Paul di Rago and Hubert Dominique Becker},

doi = {10.1016/j.molcel.2014.10.015},

issn = {1097-4164 1097-2765},

year  = {2014},

date = {2014-12-01},

journal = {Molecular cell},

volume = {56},

number = {6},

pages = {763--776},

abstract = {In eukaryotic cells, oxidative phosphorylation involves multisubunit complexes of mixed genetic origin. Assembling these complexes requires an organelle-independent synchronizing system for the proper expression of nuclear and mitochondrial genes. Here we show that proper expression of the F1FO ATP synthase (complex V) depends on a cytosolic complex (AME) made of two aminoacyl-tRNA synthetases (cERS and cMRS) attached to an anchor protein, Arc1p. When yeast cells adapt to respiration the Snf1/4 glucose-sensing pathway inhibits ARC1 expression triggering simultaneous release of cERS and cMRS. Free cMRS and cERS relocate to the nucleus and mitochondria, respectively, to synchronize nuclear transcription and mitochondrial translation of ATP synthase genes. Strains releasing asynchronously the two aminoacyl-tRNA synthetases display aberrant expression of nuclear and mitochondrial genes encoding subunits of complex V resulting in severe defects of the oxidative phosphorylation mechanism. This work shows that the AME complex coordinates expression of enzymes that require intergenomic control.},

note = {Place: United States},

keywords = {Cell Nucleus/genetics, Fungal, Gene Expression, Gene Expression Regulation, Mitochondria/genetics, Multienzyme Complexes, PPSE, Protein Multimerization, Proton-Translocating ATPases/*genetics/metabolism, RNA-Binding Proteins/physiology, Saccharomyces cerevisiae Proteins/physiology, Saccharomyces cerevisiae/enzymology/*genetics},

pubstate = {published},

tppubtype = {article}

}

@article{kwan_dermal-type_2008b,

title = {Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth},

author = {Wing-Hong Kwan and Erika Navarro-Sanchez and Hélène Dumortier and Marion Decossas and Hortense Vachon and Flavia Barreto dos Santos and Hervé W Fridman and Félix A Rey and Eva Harris and Philippe Despres and Christopher G Mueller},

doi = {10.1371/journal.pntd.0000311},

issn = {1935-2735},

year  = {2008},

date = {2008-10-01},

journal = {PLoS neglected tropical diseases},

volume = {2},

number = {10},

pages = {e311},

abstract = {BACKGROUND: An important question in dengue pathogenesis is the identity of immune cells involved in the control of dengue virus infection at the site of the mosquito bite. There is evidence that infection of immature myeloid dendritic cells plays a crucial role in dengue pathogenesis and that the interaction of the viral envelope E glycoprotein with CD209/DC-SIGN is a key element for their productive infection. Dermal macrophages express CD209, yet little is known about their role in dengue virus infection. 

METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes. 

CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.},

keywords = {Adhesion, adhesion molecules, C-Type, Cell Adhesion, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Chemistry, Cultured, Dendritic Cells, Dengue, Dengue virus, Gene Expression, Genetics, GLYCOPROTEIN, Growth, growth & development, Humans, ICAM-3, IFN ALPHA, IL-10, IL10, IMMATURE, Immunology, in situ, infection, LECTIN, Lectins, Macrophage, Macrophages, metabolism, METHOD, methods, monocyte, Monocytes, myeloid dendritic cells, pathogenesis, Phagosomes, PRODUCTION, Protein, Protein Binding, Proteins, Receptor, Receptors, Resistance, Skin, Team-Mueller, Viral Envelope Proteins, virology, virus},

pubstate = {published},

tppubtype = {article}

}

@article{kwan_dermal-type_2008,

title = {Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth},

author = {Wing-Hong Kwan and Erika Navarro-Sanchez and Hélène Dumortier and Marion Decossas and Hortense Vachon and Flavia Barreto dos Santos and Hervé W Fridman and Félix A Rey and Eva Harris and Philippe Despres and Christopher G Mueller},

doi = {10.1371/journal.pntd.0000311},

issn = {1935-2735},

year  = {2008},

date = {2008-01-01},

journal = {PLoS neglected tropical diseases},

volume = {2},

number = {10},

pages = {e311},

abstract = {BACKGROUND: An important question in dengue pathogenesis is the identity of immune cells involved in the control of dengue virus infection at the site of the mosquito bite. There is evidence that infection of immature myeloid dendritic cells plays a crucial role in dengue pathogenesis and that the interaction of the viral envelope E glycoprotein with CD209/DC-SIGN is a key element for their productive infection. Dermal macrophages express CD209, yet little is known about their role in dengue virus infection. 

METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes. 

CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.},

keywords = {C-Type, Cell Adhesion Molecules, Cell Line, Cell Surface, Cells, Cultured, Dengue, Dengue virus, Dumortier, Gene Expression, Humans, I2CT, Lectins, Macrophages, Protein Binding, Receptors, Skin, Team-Dumortier, Team-Mueller, Viral Envelope Proteins},

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{durand_lipoteichoic_2006,

title = {Lipoteichoic acid increases TLR and functional chemokine expression while reducing dentin formation in in vitro differentiated human odontoblasts},

author = {Stéphanie H Durand and Vincent Flacher and Annick Roméas and Florence Carrouel and Evelyne Colomb and Claude Vincent and Henry Magloire and Marie-Lise Couble and Françoise Bleicher and Marie-Jeanne Staquet and Serge Lebecque and Jean-Christophe Farges},

doi = {10.4049/jimmunol.176.5.2880},

issn = {0022-1767},

year  = {2006},

date = {2006-03-01},

journal = {Journal of Immunology (Baltimore, Md.: 1950)},

volume = {176},

number = {5},

pages = {2880--2887},

abstract = {Gram-positive bacteria entering the dentinal tissue during the carious process are suspected to influence the immune response in human dental pulp. Odontoblasts situated at the pulp/dentin interface are the first cells encountered by these bacteria and therefore could play a crucial role in this response. In the present study, we found that in vitro-differentiated odontoblasts constitutively expressed the pattern recognition receptor TLR1-6 and 9 genes but not TLR7, 8, and 10. Furthermore, lipoteichoic acid (LTA), a wall component of Gram-positive bacteria, triggered the activation of the odontoblasts. LTA up-regulated the expression of its own receptor TLR2, as well as the production of several chemokines. In particular, an increased amount of CCL2 and CXCL10 was detected in supernatants from LTA-stimulated odontoblasts, and those supernatants augmented the migration of immature dendritic cells in vitro compared with controls. Clinical relevance of these observations came from immunohistochemical analysis showing that CCL2 was expressed in vivo by odontoblasts and blood vessels present under active carious lesions but not in healthy dental pulps. In contrast with this inflammatory response, gene expression of major dentin matrix components (type I collagen, dentin sialophosphoprotein) and TGF-beta1 was sharply down-regulated in odontoblasts by LTA. Taken together, these data suggest that odontoblasts activated through TLR2 by Gram-positive bacteria LTA are able to initiate an innate immune response by secreting chemokines that recruit immature dendritic cells while down-regulating their specialized functions of dentin matrix synthesis and mineralization.},

keywords = {Activation, Analysis, bacteria, Biosynthesis, BLOOD, Blood Vessels, Cell Differentiation, Cells, Chemistry, chemokines, COLLAGEN, Cultured, CXCL10, cytology, Dendritic Cells, DENTAL PULP, Dentin, development, Down-Regulation, Expression, extracellular, EXTRACELLULAR MATRIX, Extracellular Matrix Proteins, function, Gene, Gene Expression, Genes, Genetics, Gram-Positive Bacteria, Human, Humans, IMMATURE, Immunology, IN VITRO, In vivo, Innate immune response, lipopolysaccharide, Lipopolysaccharides, metabolism, migration, Odontoblasts, Organ Culture Techniques, Pharmacology, physiology, PRODUCTION, Protein, Proteins, Receptor, recognition, synthesis, Team-Mueller, Teichoic Acids, TLR7, Toll-Like Receptor 2, Up-Regulation},

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{georgel_drosophila_2001,

title = {Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis},

author = {Philippe Georgel and S Naitza and Christine Kappler and Dominique Ferrandon and Daniel Zachary and C Swimmer and C Kopczynski and G Duyk and Jean-Marc Reichhart and Jules A Hoffmann},

issn = {1534-5807},

year  = {2001},

date = {2001-10-01},

journal = {Dev. Cell},

volume = {1},

number = {4},

pages = {503--514},

abstract = {We report the molecular characterization of the immune deficiency (imd) gene, which controls antibacterial defense in Drosophila. imd encodes a protein with a death domain similar to that of mammalian RIP (receptor interacting protein), a protein that plays a role in both NF-kappaB activation and apoptosis. We show that imd functions upstream of the DmIKK signalosome and the caspase DREDD in the control of antibacterial peptide genes. Strikingly, overexpression of imd leads to constitutive transcription of these genes and to apoptosis, and both effects are blocked by coexpression of the caspase inhibitor P35. We also show that imd is involved in the apoptotic response to UV irradiation. These data raise the possibility that antibacterial response and apoptosis share common control elements in Drosophila.},

keywords = {Animals, Anti-Infective Agents, Apoptosis, Bacterial Infections, Caspases, Chromosome Mapping, Cysteine Proteinase Inhibitors, DNA Damage, Female, ferrandon, Gene Expression, hoffmann, I-kappa B Kinase, Immunocompromised Host, In Situ Nick-End Labeling, Insect Proteins, M3i, Male, Mutation, Phenotype, Protein Structure, Protein-Serine-Threonine Kinases, reichhart, Tertiary},

pubstate = {published},

tppubtype = {article}

}

@article{boulanger_immune_2001,

title = {Immune response of Drosophila melanogaster to infection with the flagellate parasite Crithidia spp},

author = {Nathalie Boulanger and Laurence Ehret-Sabatier and R Brun and Daniel Zachary and Philippe Bulet and Jean-Luc Imler},

issn = {0965-1748},

year  = {2001},

date = {2001-02-01},

journal = {Insect Biochemistry and Molecular Biology},

volume = {31},

number = {2},

pages = {129--137},

abstract = {Insects are able to recognize invading microorganisms and to mount an immune response to bacterial and fungal infections. Recently, the fruitfly Drosophila melanogaster has emerged as a promising invertebrate model to investigate innate immunity because of its well-characterized genetics. Insects are also vectors of numerous parasites which can trigger an immune response. We have investigated the interaction of Drosophila melanogaster with the flagellate protozoan Crithidia spp. We show that a per os parasitic infection triggers the synthesis of several antimicrobial peptides. By reverse phase HPLC and mass spectrometry, peptides were shown to be present in the hemolymph and not in the gut tissue, suggesting the presence of immune messengers between the site of the infection, namely the gut, and the fat body, the main site of synthesis for antimicrobial peptides. Interestingly, we have identified one molecule which is specifically induced in the hemolymph after infection with Crithidia, but not with bacteria, suggesting that Drosophila can discriminate between pathogens. When flagellates were injected into the hemolymph, a low synthesis of antimicrobial peptides was observed together with phagocytosis of parasites by circulating hemocytes. The data presented here suggest that Drosophila-Crithidia spp. represents an interesting model to study host defense against protozoan parasites.},

keywords = {Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Crithidia, Defensins, Gene Expression, Glycopeptides, Hemocytes, imler, Insect Proteins, M3i, Phagocytosis},

pubstate = {published},

tppubtype = {article}

}

@article{lowenberger_insect_1999,

title = {Insect immunity: molecular cloning, expression, and characterization of cDNAs and genomic DNA encoding three isoforms of insect defensin in Aedes aegypti},

author = {C A Lowenberger and C T Smartt and Philippe Bulet and M T Ferdig and D W Severson and Jules A Hoffmann and B M Christensen},

issn = {0962-1075},

year  = {1999},

date = {1999-02-01},

journal = {Insect Mol. Biol.},

volume = {8},

number = {1},

pages = {107--118},

abstract = {Aedes aegypti were immune activated by injection with bacteria, and the expression of insect defensins was measured over time. Northern analyses indicated that defensin transcriptional activity continued for at least 21 days after bacterial injection, and up to 10 days after saline inoculation. Mature defensin levels in the haemolymph reached approximately 45 microM at 24 h post inoculation. cDNAs encoding the preprodefensins of three previously described mature Ae. aegypti defensins were amplified by PCR, cloned and sequenced. Genomic clones were amplified using primers designed against the cDNA sequence. Sequence comparison indicates that there is significant inter- and intra-isoform variability in the signal peptide and prodefensin sequences of defensin genes. Preprodefensin sequences of isoforms A and B are very similar, consisting of a signal peptide region of twenty amino acids, a prodefensin region of thirty-eight amino acids and a forty amino acid mature peptide domain. The sequence encoding isoform C is significantly different, comprising a signal peptide region of twenty-three amino acids, a prodefensin region of thirty-six amino acids, and the mature protein domain of forty amino acids. Analysis of the genomic clones of each isoform revealed one intron spatially conserved in the prodefensin region of all sequences. The intron in isoforms A and B is 64 nt long, and except for a 4 nt substitution in one clone, these intron sequences are identical. The intron in isoform C is 76 nt long and does not share significant identity with the intron sequences of isoforms A or B. The defensin gene mapped to chromosome 3, between two known loci, blt and LF168.},

keywords = {Aedes, Amino Acid, Animals, Base Sequence, Blotting, Chromosome Mapping, Cloning, Complementary, Defensins, DNA, Gene Expression, Hemolymph, hoffmann, M3i, Molecular, Northern, Protein Isoforms, Proteins, Sequence Homology},

pubstate = {published},

tppubtype = {article}

}

@article{dimarcq_treatment_1997,

title = {Treatment of l(2)mbn Drosophila tumorous blood cells with the steroid hormone ecdysone amplifies the inducibility of antimicrobial peptide gene expression},

author = {Jean-Luc Dimarcq and Jean-Luc Imler and R Lanot and Alan R B Ezekowitz and Jules A Hoffmann and C A Janeway and Marie Lagueux},

issn = {0965-1748},

year  = {1997},

date = {1997-10-01},

journal = {Insect Biochemistry and Molecular Biology},

volume = {27},

number = {10},

pages = {877--886},

abstract = {Insects rely on both humoral and cellular mechanisms to defend themselves against microbial infections. The humoral response involves synthesis of a battery of potent antimicrobial peptides by the fat body and, to a lesser extent, by blood cells. The cellular response on the other hand consists of phagocytosis of small microorganisms and melanization and encapsulation of larger parasites. The l(2)mbn cell line, established from tumorous larval hemocytes, represents a system of choice to dissect the molecular events controlling cellular immunity. We report here that l(2)mbn cells can be efficiently induced to differentiate in adherent, macrophage-like cells by treatment with 20-hydroxyecdysone. Ecdysone treatment increases both the phagocytic capacity of l(2)mbn cells and their competence to express antimicrobial genes in response to immune challenge. We also report that expression of several regulatory molecules thought to be involved in the immune response is up-regulated by ecdysone in l(2)mbn cells.},

keywords = {Animals, Bacterial Infections, Cellular, Ecdysone, Gene Expression, Genes, Hemocytes, Hemolymph, hoffmann, imler, Immunity, Insect, M3i, Macrophages, Peptide Biosynthesis, Phagocytosis},

pubstate = {published},

tppubtype = {article}

}

@article{richman_inducible_1996,

title = {Inducible immune factors of the vector mosquito Anopheles gambiae: biochemical purification of a defensin antibacterial peptide and molecular cloning of preprodefensin cDNA},

author = {A M Richman and Philippe Bulet and Charles Hetru and Carolina Barillas-Mury and Jules A Hoffmann and Fotis C Kafalos},

issn = {0962-1075},

year  = {1996},

date = {1996-08-01},

journal = {Insect Mol. Biol.},

volume = {5},

number = {3},

pages = {203--210},

abstract = {Larvae of the mosquito vector of human malaria, Anopheles gambiae, were inoculated with bacteria and extracts were biochemically fractionated by reverse-phase HPLC. Multiple induced polypeptides and antibacterial activities were observed following bacterial infection, including a member of the insect defensin family of antibacterial proteins. A cDNA encoding An. gambiae preprodefensin was isolated using PCR primers based on phylogenetically conserved sequences. The mature peptide is highly conserved, but the signal and propeptide segments are not, relative to corresponding defensin sequences of other insects. Defensin expression is induced in response to bacterial infection, in both adult and larval stages. In contrast, pupae express defensin mRNA constitutively. Defensin expression may prove a valuable molecular marker to monitor the An. gambiae host response to infection by parasitic protozoa of medical importance.},

keywords = {Amino Acid, Animals, Anopheles, Base Sequence, Blood Bactericidal Activity, Blood Proteins, Cloning, Complementary, Defensins, DNA, Escherichia coli, Female, Gene Expression, Genes, hoffmann, Insect, Insect Vectors, Larva, M3i, Micrococcus luteus, Molecular, Sequence Homology},

pubstate = {published},

tppubtype = {article}

}

@article{lemaitre_dorsoventral_1996,

title = {The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults},

author = {Bruno Lemaitre and E Nicolas and Lydia Michaut and Jean-Marc Reichhart and Jules A Hoffmann},

issn = {0092-8674},

year  = {1996},

date = {1996-01-01},

journal = {Cell},

volume = {86},

number = {6},

pages = {973--983},

abstract = {The cytokine-induced activation cascade of NF-kappaB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB). Here we demonstrate that these parallels extend to the immune response of Drosophila. In particular, the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults. We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways.},

keywords = {Animals, Antifungal Agents, Cell Surface, DNA-Binding Proteins, Fungi, Gene Expression, Genes, hoffmann, Insect, Insect Hormones, Insect Proteins, M3i, Membrane Glycoproteins, MHC Class II, Mutation, Mycoses, NF-kappa B, Phosphoproteins, Proteins, Receptors, reichhart, Signal Transduction, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{dimarcq_characterization_1994,

title = {Characterization and transcriptional profiles of a Drosophila gene encoding an insect defensin. A study in insect immunity},

author = {Jean-Luc Dimarcq and Danièle Hoffmann and Marie Meister and Philippe Bulet and R Lanot and Jean-Marc Reichhart and Jules A Hoffmann},

issn = {0014-2956},

year  = {1994},

date = {1994-04-01},

journal = {Eur. J. Biochem.},

volume = {221},

number = {1},

pages = {201--209},

abstract = {Insect defensins are a family of 4-kDa, cationic, inducible antibacterial peptides which bear six cysteine residues engaged in three intramolecular disulfide bridges. They owe their name to certain sequence similarities with defensins from mammalian neutrophiles and macrophages. We report the characterization of a novel defensin isoform from Drosophila and the cloning of the gene encoding a preprodefensin. The gene, which is intronless and present in a single copy/haploid genome, maps at position 46CD on the right arm of the second chromosome. The analysis of the upstream region of the gene reveals the presence of multiple putative cis-regulatory sequences similar to mammalian regulatory motifs of acute-phase-response genes. Transcriptional profiles indicate that the Drosophila defensin gene is induced by bacterial challenge with acute-phase kinetics. It is also expressed in the absence of immune challenge during metamorphosis. These and other data on the Drosophila defensin gene lead us to suggest that insect and mammalian defensins have evolved independently.},

keywords = {Animals, Base Sequence, Blood Proteins, Chromosome Mapping, Cloning, Complementary, Defensins, DNA, Gene Expression, Genetic, Gram-Positive Bacteria, hoffmann, Larva, M3i, Molecular, Molecular Structure, Nucleic Acid, Protein Precursors, Regulatory Sequences, reichhart, Transcription},

pubstate = {published},

tppubtype = {article}

}

@article{reichhart_expression_1993,

title = {Expression and nuclear translocation of the rel/NF-kappa B-related morphogen dorsal during the immune response of Drosophila},

author = {Jean-Marc Reichhart and Philippe Georgel and Marie Meister and Bruno Lemaitre and Christine Kappler and Jules A Hoffmann},

issn = {0764-4469},

year  = {1993},

date = {1993-01-01},

journal = {C. R. Acad. Sci. III, Sci. Vie},

volume = {316},

number = {10},

pages = {1218--1224},

abstract = {The rel/NF-kappa B-related morphogen dorsal is a maternally expressed gene which is involved in the control of the dorso-ventral axis during early embryogenesis of Drosophila. We show that this gene is also expressed in the fat body of larvae and adults of Drosophila as well as in a tumorous blood cell line: its expression is noticeably enhanced upon bacterial (or lipopolysaccharide) challenge. This challenge also induces within 15-30 min a nuclear translocation of the dorsal protein. The genes encoding inducible antibacterial peptides in Drosophila contain kappa B-related nucleotide sequences and we show that the dorsal protein can bind to such motifs and sequence-specifically transactivate a reporter gene in co-transfection experiments with a Drosophila cell line. However, in dl1 mutants, in the absence of dorsal protein, the genes encoding antibacterial peptides retain their inducibility, suggesting a multifactorial control. The results indicate that in addition to its role in embryogenesis, dorsal is involved in the immune response of Drosophila. They also strengthen the analogy between the mammalian acute phase response and the insect immune response.},

keywords = {Animals, Blotting, Cellular, Gene Expression, Genes, Genetic, hoffmann, Immunity, Insect, M3i, NF-kappa B, Northern, reichhart, translocation, Zygote},

pubstate = {published},

tppubtype = {article}

}

@article{dimarcq_insect_1990,

title = {Insect immunity: expression of the two major inducible antibacterial peptides, defensin and diptericin, in Phormia terranovae},

author = {Jean-Luc Dimarcq and Daniel Zachary and Jules A Hoffmann and Danièle Hoffmann and Jean-Marc Reichhart},

issn = {0261-4189},

year  = {1990},

date = {1990-08-01},

journal = {EMBO J.},

volume = {9},

number = {8},

pages = {2507--2515},

abstract = {Injections of low doses of bacteria into larvae of Phormia terranovae induce the appearance of potent bactericidal peptides in the blood, among which predominate the anti-Gram positive insect defensins and the anti-Gram negative diptericins. Insect defensins show significant homologies to mammalian (including human) microbicidal peptides present in polymorphonuclear leukocytes and macrophages. We report the molecular cloning of cDNAs and primer extension studies which indicate that insect defensin is produced as a prepro-peptide yielding mature defensin A (40 residues) after cleavage of a putative signal peptide (23 residues) and a prosequence (34 residues). Previous studies have established that diptericin (82 residues) is matured from a pre-peptide by cleavage of a putative signal peptide (19 residues) and C-terminal amidation. Using oligonucleotide probes complementary to the sequences of the mRNAs for defensin and diptericin, we show by in situ hybridization that both antibacterial peptides are concomitantly synthesized by the same cells: thrombocytoids, a specialized blood cell type, and adipocytes. Transcriptional studies based on hybridization of RNAs to cDNAs of defensin and diptericin indicate that the transcription of both genes is induced regardless of the nature of the stimulus (injection of Gram positive or Gram negative bacteria, lipopolysaccharides). Even a sterile injury applied to axenically raised larvae is efficient in inducing the transcription of both genes suggesting that the local disruption of the integument aspecifically initiates a signalling mechanism which the thrombocytoids and the adipocytes are able to interpret. The transcription of immune genes is relatively short lived and a second challenge yields a response similar to that of the first stimulus, indicating that the experimental insects do not keep a 'memory' of their first injection.},

keywords = {Animals, Anti-Bacterial Agents, Base Sequence, Blood Proteins, Cloning, Defensins, Diptera, Gene Expression, hoffmann, Insect Hormones, Insect Proteins, Larva, M3i, Molecular, Nucleic Acid Hybridization, Oligonucleotide Probes, Protein Conformation, reichhart},

pubstate = {published},

tppubtype = {article}

}