ARN

@article{liu_drosophila_2012,

title = {Drosophila EYA regulates the immune response against DNA through an evolutionarily conserved threonine phosphatase motif},

author = {Xi Liu and Teruyuki Sano and Yongsheng Guan and Shigekazu Nagata and Jules A Hoffmann and Hidehiro Fukuyama},

doi = {10.1371/journal.pone.0042725},

issn = {1932-6203},

year  = {2012},

date = {2012-01-01},

journal = {PLoS ONE},

volume = {7},

number = {8},

pages = {e42725},

abstract = {Innate immune responses against DNA are essential to counter both pathogen infections and tissue damages. Mammalian EYAs were recently shown to play a role in regulating the innate immune responses against DNA. Here, we demonstrate that the unique Drosophila eya gene is also involved in the response specific to DNA. Haploinsufficiency of eya in mutants deficient for lysosomal DNase activity (DNaseII) reduces antimicrobial peptide gene expression, a hallmark for immune responses in flies. Like the mammalian orthologues, Drosophila EYA features a N-terminal threonine and C-terminal tyrosine phosphatase domain. Through the generation of a series of mutant EYA fly strains, we show that the threonine phosphatase domain, but not the tyrosine phosphatase domain, is responsible for the innate immune response against DNA. A similar role for the threonine phosphatase domain in mammalian EYA4 had been surmised on the basis of in vitro studies. Furthermore EYA associates with IKKβ and full-length RELISH, and the induction of the IMD pathway-dependent antimicrobial peptide gene is independent of SO. Our data provide the first in vivo demonstration for the immune function of EYA and point to their conserved immune function in response to endogenous DNA, throughout evolution.},

keywords = {Amino Acid, Animals, Blotting, Conserved Sequence, Endodeoxyribonucleases, Eye Proteins, hoffmann, Immunoprecipitation, M3i, Phosphoprotein Phosphatases, Sequence Homology, Transcription Factors, Western},

pubstate = {published},

tppubtype = {article}

}

@article{baeza_garcia_involvement_2010,

title = {Involvement of the cytokine MIF in the snail host immune response to the parasite Schistosoma mansoni},

author = {Alvaro Baeza Garcia and Raymond J Pierce and Benjamin Gourbal and Elisabeth Werkmeister and Dominique Colinet and Jean-Marc Reichhart and Colette Dissous and Christine Coustau},

doi = {10.1371/journal.ppat.1001115},

issn = {1553-7374},

year  = {2010},

date = {2010-01-01},

journal = {PLoS Pathog.},

volume = {6},

number = {9},

pages = {e1001115},

abstract = {We have identified and characterized a Macrophage Migration Inhibitory Factor (MIF) family member in the Lophotrochozoan invertebrate, Biomphalaria glabrata, the snail intermediate host of the human blood fluke Schistosoma mansoni. In mammals, MIF is a widely expressed pleiotropic cytokine with potent pro-inflammatory properties that controls cell functions such as gene expression, proliferation or apoptosis. Here we show that the MIF protein from B. glabrata (BgMIF) is expressed in circulating immune defense cells (hemocytes) of the snail as well as in the B. glabrata embryonic (Bge) cell line that has hemocyte-like features. Recombinant BgMIF (rBgMIF) induced cell proliferation and inhibited NO-dependent p53-mediated apoptosis in Bge cells. Moreover, knock-down of BgMIF expression in Bge cells interfered with the in vitro encapsulation of S. mansoni sporocysts. Furthermore, the in vivo knock-down of BgMIF prevented the changes in circulating hemocyte populations that occur in response to an infection by S. mansoni miracidia and led to a significant increase in the parasite burden of the snails. These results provide the first functional evidence that a MIF ortholog is involved in an invertebrate immune response towards a parasitic infection and highlight the importance of cytokines in invertebrate-parasite interactions.},

keywords = {Amino Acid, Animals, Apoptosis, Biomphalaria, Blotting, Cell Proliferation, Cells, Cricetinae, Cultured, Hemocytes, Host-Parasite Interactions, Humans, Liver, M3i, Macrophage Migration-Inhibitory Factors, messenger, Oocysts, Recombinant Proteins, reichhart, Reverse Transcriptase Polymerase Chain Reaction, RNA, Schistosoma mansoni, Schistosomiasis mansoni, Sequence Homology, Small Interfering, Western},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {IgG reactivity with a 100-kDa tissue and endothelial cell antigen identified as topoisomerase 1 distinguishes between limited and diffuse systemic sclerosis patients},

author = { P. Garcia de la Pena-Lefebvre and Y. Chanseaud and M. C. Tamby and J. Reinbolt and F. Batteux and Y. Allanore and A. Kahan and O. Meyer and O. Benveniste and O. Boyer and L. Guillevin and M. C. Boissier and L. Mouthon},

year  = {2004},

date = {2004-01-01},

journal = {Clin Immunol},

volume = {111},

number = {3},

pages = {241-51},

abstract = {We have analyzed antibody (Ab) reactivities of patients with limited systemic sclerosis (SSc) and anti-centromere Ab, patients with diffuse SSc and anti-topoisomerase 1 (anti-topo 1) Ab, patients with diffuse SSc without anti-topo 1 or anti-centromere Ab and age- and gender-matched healthy controls with normal human tissue and endothelial cell (EC) antigens. IgG reactivities with tissue antigens differed significantly between patients with anti-topo 1 Ab and patients with anti-centromere Ab. One 100-kDa band identified as topoisomerase 1 in macrovascular and microvascular EC extracts was recognized by IgG from patients with anti-topo 1 Ab and 50% of patients without specific Ab. IgG from patients with limited SSc and anti-centromere Ab, but not those of other patients or controls specifically recognized a 80-kDa band only in microvascular EC. Our results indicate that Ab from patients with limited or diffuse SSc with or without anti-topo 1 Ab exhibit specific and mutually exclusive reactivity patterns.},

note = {1521-6616 

Journal Article},

keywords = {Aged, Assay, Autoantibodies/*analysis, Blotting, Cells/*immunology, Centromere/immunology, DNA, EHRESMANN, Electrophoresis, Endothelial, Enzyme-Linked, Female, G/analysis, Gel, Gov't, Human, I/*immunology, Immunoglobulin, Immunosorbent, M/analysis, Male, Middle, Non-U.S., Polyacrylamide, Scleroderma, Support, Systemic/*immunology, Topoisomerases, Type, Western},

pubstate = {published},

tppubtype = {article}

}

@article{munier_pvf2_2002,

title = {PVF2, a PDGF/VEGF-like growth factor, induces hemocyte proliferation in Drosophila larvae},

author = {Anne-Isabelle Munier and Daniel Doucet and Emmanuel Perrodou and Daniel Zachary and Marie Meister and Jules A Hoffmann and Charles A Janeway and Marie Lagueux},

doi = {10.1093/embo-reports/kvf242},

issn = {1469-221X},

year  = {2002},

date = {2002-12-01},

journal = {EMBO Rep.},

volume = {3},

number = {12},

pages = {1195--1200},

abstract = {Blood cells play a crucial role in both morphogenetic and immunological processes in Drosophila, yet the factors regulating their proliferation remain largely unknown. In order to address this question, we raised antibodies against a tumorous blood cell line and identified an antigenic determinant that marks the surface of prohemocytes and also circulating plasmatocytes in larvae. This antigen was identified as a Drosophila homolog of the mammalian receptor for platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF). The Drosophila receptor controls cell proliferation in vitro. By overexpressing in vivo one of its putative ligands, PVF2, we induced a dramatic increase in circulating hemocytes. These results identify the PDGF/VEGF receptor homolog and one of its ligands as important players in Drosophila hematopoiesis.},

keywords = {Animals, Antibodies, Blotting, Cell Differentiation, Hemocytes, hoffmann, Immunohistochemistry, Larva, ligands, M3i, Platelet-Derived Growth Factor, Receptors, Vascular Endothelial Growth Factor, Western},

pubstate = {published},

tppubtype = {article}

}

@article{kambris_tissue_2002,

title = {Tissue and stage-specific expression of the Tolls in Drosophila embryos},

author = {Zakaria Kambris and Jules A Hoffmann and Jean-Luc Imler and Maria Capovilla},

issn = {1567-133X},

year  = {2002},

date = {2002-12-01},

journal = {Gene expression patterns: GEP},

volume = {2},

number = {3-4},

pages = {311--317},

abstract = {The Drosophila transmembrane receptor Toll plays a key role in specifying the dorsoventral axis of the embryo. At later stages of development, it controls the immune response of the fly to fungal and Gram-positive bacterial infections. The Drosophila genome has a total of nine Toll-like genes, including the previously characterized Toll (Toll-1) and 18-wheeler (Toll-2). Here we describe the embryonic expression patterns of the seven Toll-like genes Toll-3 through Toll-9. We find that these genes have distinct expression domains and that their expression is dynamically changing throughout embryonic development. This complex and tissue-specific regulation of Toll-like gene expression strongly suggests a role in embryonic development for most Drosophila Tolls. The evolving picture on the Toll family members in Drosophila contrasts with that of mammalian Toll-like receptors, which are predominantly expressed in immune responsive cells where their activation occurs via microbial structural determinants.},

keywords = {Animals, Blotting, Cell Surface, Gene Expression Profiling, hoffmann, imler, Larva, M3i, Multigene Family, Northern, Receptors, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{tauszig_toll-related_2000,

title = {Toll-related receptors and the control of antimicrobial peptide expression in Drosophila},

author = {Servane Tauszig and Emmanuelle Jouanguy and Jules A Hoffmann and Jean-Luc Imler},

doi = {10.1073/pnas.180130797},

issn = {0027-8424},

year  = {2000},

date = {2000-09-01},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

volume = {97},

number = {19},

pages = {10520--10525},

abstract = {Insects defend themselves against infectious microorganisms by synthesizing potent antimicrobial peptides. Drosophila has appeared in recent years as a favorable model to study this innate host defense. A genetic analysis of the regulation of the antifungal peptide drosomycin has demonstrated a key role for the transmembrane receptor Toll, which prompted the search for mammalian homologs. Two of these, Toll-like receptor (TLR)2 and TLR4, recently were shown to play a critical role in innate immunity against bacteria. Here we describe six additional Toll-related genes (Toll-3 to Toll-8) in Drosophila in addition to 18-wheeler. Two of these genes, Toll-3 and Toll-4, are expressed at a low level. Toll-6, -7, and -8, on the other hand, are expressed at high levels during embryogenesis and molting, suggesting that, like Toll and 18w, they perform developmental functions. Finally, Toll-5 is expressed only in larvae and adults. By using chimeric constructs, we have tested the capacity of the signaling Toll/IL-1R homology domains of these receptors to activate antimicrobial peptide promoters and found that only Toll and Toll-5 can activate the drosomycin promoter in transfected cells, thus demonstrating specificity at the level of the Toll/IL-1R homology domain. In contrast, none of these constructs activated antibacterial peptide promoters, suggesting that Toll-related receptors are not involved in the regulation of antibacterial peptide expression. This result was independently confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide.},

keywords = {Amino Acid, Animals, Anti-Bacterial Agents, Blotting, Cell Line, Cell Surface, hoffmann, imler, M3i, Membrane Glycoproteins, Multigene Family, Northern, Peptides, Receptors, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptor 5, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@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{dumortier_mhc_1999,

title = {MHC class II gene associations with autoantibodies to U1A and SmD1 proteins},

author = {H Dumortier and M Abbal and M Fort and J P Briand and A Cantagrel and S Muller},

doi = {10.1093/intimm/11.2.249},

issn = {0953-8178},

year  = {1999},

date = {1999-01-01},

journal = {International Immunology},

volume = {11},

number = {2},

pages = {249--257},

abstract = {Autoantibodies against U small nuclear ribonucleoproteins (snRNP) are frequently present in the serum of patients with systemic rheumatic diseases, and have been reported to be associated with HLA-DR and -DQ genes. To better define the role of HLA genes in the production of such antibodies, we studied immunogenetic associations with autoantibodies reacting with U1 RNP, U1A and SmD1 proteins, and synthetic peptides containing immunodominant linear epitopes of these proteins. Only two out of the 15 overlapping peptides of U1A (i.e. peptides 35-58 and 257-282) and three of 11 peptides of SmD1 (i.e. peptides 1-20, 44-67 and 97-119) were significantly recognized by patients' sera selected on the basis of their antibody positivity with RNP in immunodiffusion. The distribution of DRB1, DQB1 and DPB1 alleles among the anti-RNP antibody-positive patients (n = 28) and healthy control subjects was similar. Antibodies against U1A (tested in Western immunoblotting with HeLa cell extracts) were positively associated to DRB1*06 allele; antibodies reacting with SmD1 peptide 44-67 were negatively associated to DRB1*02 and DQB1*0602 alleles. No association was found between DPB1 alleles and antibodies reacting with U1A and SmD1 antigens. This first study reporting an association between autoantibodies reacting with U1A and SmD1 proteins (and peptides of these proteins), and immunogenetic markers suggest that the production of antibody subsets directed against different components (or regions of these proteins) bound to the same snRNP particle is associated with distinct MHC class II alleles.},

keywords = {Alleles, Antibody Specificity, Autoantibodies, Autoantigens, Autoimmune Diseases, Blotting, Dumortier, Enzyme-Linked Immunosorbent Assay, Genes, HLA-DP Antigens, HLA-DP beta-Chains, HLA-DQ Antigens, HLA-DQ beta-Chains, HLA-DR Antigens, HLA-DRB1 Chains, Humans, I2CT, MHC Class II, Peptides, Rheumatic Diseases, Ribonucleoprotein, Ribonucleoproteins, RNA-Binding Proteins, Small Nuclear, snRNP Core Proteins, Team-Dumortier, U1 Small Nuclear, Western},

pubstate = {published},

tppubtype = {article}

}

@article{lowenberger_aedes_1996,

title = {Aedes aegypti: induced antibacterial proteins reduce the establishment and development of Brugia malayi},

author = {C A Lowenberger and M T Ferdig and Philippe Bulet and S Khalili and Jules A Hoffmann and B M Christensen},

doi = {10.1006/expr.1996.0066},

issn = {0014-4894},

year  = {1996},

date = {1996-07-01},

journal = {Exp. Parasitol.},

volume = {83},

number = {2},

pages = {191--201},

abstract = {The effect of host immune activation on the development of Brugia malayi in one susceptible and four refractory strains of Aedes aegypti and in Armigeres subalbatus was assessed. A. aegypti that were immune activated by the injection of saline or bacteria 24 hr before feeding on a B. malayi-infected gerbil had significantly reduced prevalences and mean intensities of infection from those of naive controls when exposed to bloodmeals with low (105 mf/20 microliters) and medium (160 mf/20 microliters) microfilaremias. At a higher microfilaremia (237 mf/20 microliters) there were no significant differences in mean intensities, suggesting that the number of parasites ingested may affect the host's ability to mount an effective defense response. Because the major immune proteins in A. aegypti are defensins, we did Northern analyses of fat body RNA 8 hr after immune activation or bloodfeeding. All mosquitoes demonstrated rapid transcriptional activity for defensins following immune activation by intrathoracic inoculation with either saline or bacteria. However, no strain of A. aegypti, susceptible or refractory to B. malayi, nor Ar. subalbatus produced defensin transcripts after bloodfeeding on an uninfected or a B. malayi-infected gerbil. These data suggest that inducible immune proteins of mosquitoes can reduce the prevalence and mean intensity of infections with ingested parasites, but these proteins are not expressed routinely after parasite ingestion and midgut penetration and probably do not contribute to existing refractory mechanisms. Immune proteins such as defensins, however, represent potential candidates to genetically engineer mosquitoes for resistance to filarial worms.},

keywords = {Aedes, Analysis of Variance, Animals, Anti-Bacterial Agents, Base Sequence, Blood Proteins, Blotting, Brugia malayi, Culicidae, Defensins, DNA, Escherichia coli, Fat Body, Genetic, Gerbillinae, hoffmann, M3i, Micrococcus luteus, Microfilaria, Northern, RNA, 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{,

title = {The major RNA in prosomes of HeLa cells and duck erythroblasts is tRNA(Lys,3)},

author = { H. G. Nothwang and O. Coux and G. Keith and I. Silva-Pereira and K. Scherrer},

year  = {1992},

date = {1992-01-01},

journal = {Nucleic Acids Res},

volume = {20},

number = {8},

pages = {1959-65},

abstract = {Two-dimensional gel electrophoresis of HeLa cell prosomal RNAs, 3'-end labeled by RNA ligase, revealed one prominent spot. Determination of a partial sequence at the 3'-end indicated full homology to the 18 nucleotides at the 3'-end of tRNA(Lys,3) from rabbit, the bovine and the human species. An oligonucleotide complementary to the 3'-end of tRNA(Lys,3) hybridized on Northern blots with prosomal RNA from both HeLa cells and duck erythroblasts. In two-dimensional PAGE, the major pRNA of HeLa cells co-migrated with bovine tRNA(Lys,3). Reconstitution of the CCA 3'-end of RNA from both human and duck prosomes, by tRNA-nucleotidyl-transferase, confirmed the tRNA character of this type of RNA. Furthermore, it revealed at least one additional tRNA band about 85 nt long among the prosomal RNA from both species. Finally, confirming an original property of prosomal RNA, we show that in vitro synthesized tRNA(Lys,3) hybridizes stably to duck globin mRNA, and to poly(A)(+)- and poly(A)(-)-RNA from HeLa cells.},

note = {0305-1048 

Journal Article},

keywords = {Animals, Base, Blotting, Cells, Data, Ducks, effects, Electrophoresis, Erythroblasts, Gel, Gov't, Hela, Human, Lys/*analysis/metabolism, Molecular, Non-U.S., Northern, Nucleotidyltransferases/metabolism, Ribonucleoproteins/*chemistry/drug, RNA, Sequence, Support, Transfer, Two-Dimensional, Zinc/pharmacology},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {Pleiotropic effect of a point mutation in the yeast SUP4-o tRNA gene: in vivo pre-tRNA processing in S. cerevisiae},

author = { M. L. Wilhelm and G. Keith and C. Fix and F. X. Wilhelm},

year  = {1992},

date = {1992-01-01},

journal = {Nucleic Acids Res},

volume = {20},

number = {4},

pages = {791-6},

abstract = {The expression of mutant tyrosine-inserting ochre suppressor SUP4-o tRNA genes in vivo in S. cerevisiae was examined as a basis for further studies of tRNA transcription and processing. In vivo yeast precursor tRNAs have been identified by filter hybridization and primer extension analysis. We have previously shown that a mutant SUP4-o tRNA gene with a C52----A52 transversion at positive 52 (C52----A52(+IVS) allele) was transcribed but that the primary transcript was not processed correctly. We show here that 5' and 3' end processing as well as splicing are defective for this mutant but that the 5' end processing is restored when the intron is removed from the gene by oligonucleotide directed mutagenesis (C52----A52(-IVS) allele). Our results imply that the C52----A52 transversion by itself cannot account for the lack of susceptibility to RNase P cleavage but that the overall tertiary structure of the mutant tRNA precursor is destabilized by the intron/anticodon stem. A second consequence of the C52----A52 transversion is to prevent complete maturation of the tRNA precursor at its 3' end since intermediates containing incompletely processed 3' trailers accumulate in the yeast cells transformed with the C52----A52(-IVS) allele. A correct structure of the T stem might therefore define a structural feature required for the recognition of the 3' processing activity.},

note = {0305-1048 

Journal Article},

keywords = {Base, Blotting, cerevisiae/*genetics/metabolism, Data, Fungal/*genetics, Fungal/genetics/metabolism, Genes, Introns/genetics, Molecular, Mutation/genetics, Northern, Precursors/*metabolism, RNA, Saccharomyces, Sequence, Suppressor/*genetics, Transfer, Tyr/*genetics/metabolism},

pubstate = {published},

tppubtype = {article}

}