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PLoS pathogens, 2015-04, Vol.11 (4), p.e1004876-e1004876
2015
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Autor(en) / Beteiligte
Titel
An effector Peptide family required for Drosophila toll-mediated immunity
Ist Teil von
  • PLoS pathogens, 2015-04, Vol.11 (4), p.e1004876-e1004876
Ort / Verlag
United States: Public Library of Science
Erscheinungsjahr
2015
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
  • In Drosophila melanogaster, recognition of an invading pathogen activates the Toll or Imd signaling pathway, triggering robust upregulation of innate immune effectors. Although the mechanisms of pathogen recognition and signaling are now well understood, the functions of the immune-induced transcriptome and proteome remain much less well characterized. Through bioinformatic analysis of effector gene sequences, we have defined a family of twelve genes - the Bomanins (Boms) - that are specifically induced by Toll and that encode small, secreted peptides of unknown biochemical activity. Using targeted genome engineering, we have deleted ten of the twelve Bom genes. Remarkably, inactivating these ten genes decreases survival upon microbial infection to the same extent, and with the same specificity, as does eliminating Toll pathway function. Toll signaling, however, appears unaffected. Assaying bacterial load post-infection in wild-type and mutant flies, we provide evidence that the Boms are required for resistance to, rather than tolerance of, infection. In addition, by generating and assaying a deletion of a smaller subset of the Bom genes, we find that there is overlap in Bom activity toward particular pathogens. Together, these studies deepen our understanding of Toll-mediated immunity and provide a new in vivo model for exploration of the innate immune effector repertoire.
Sprache
Englisch
Identifikatoren
ISSN: 1553-7374, 1553-7366
eISSN: 1553-7374
DOI: 10.1371/journal.ppat.1004876
Titel-ID: cdi_plos_journals_1685368829
Format
Schlagworte
Animals, Antimicrobial Cationic Peptides - chemistry, Antimicrobial Cationic Peptides - genetics, Antimicrobial Cationic Peptides - metabolism, Antimicrobial Cationic Peptides - secretion, Bacterial infections, Candida glabrata - immunology, Candida glabrata - physiology, Computational Biology, DNA sequencing, Drosophila, Drosophila melanogaster - immunology, Drosophila melanogaster - metabolism, Drosophila melanogaster - microbiology, Drosophila Proteins - chemistry, Drosophila Proteins - genetics, Drosophila Proteins - metabolism, Drosophila Proteins - secretion, Enterococcus faecalis - immunology, Enterococcus faecalis - physiology, Experiments, Fusarium - immunology, Fusarium - physiology, Gene Deletion, Gene expression, Gene Expression Regulation, Genetic aspects, Genetic engineering, Genomes, Genotype & phenotype, Health aspects, Host-Pathogen Interactions, Immune system, Immunity, Innate, Infections, Insects, Kaplan-Meier Estimate, Male, Mass spectrometry, Methods, Peptide Fragments - chemistry, Peptide Fragments - genetics, Peptide Fragments - metabolism, Peptide Fragments - secretion, Peptides, Peptides - chemistry, Peptides - genetics, Peptides - metabolism, Peptides - secretion, Protein Isoforms - chemistry, Protein Isoforms - genetics, Protein Isoforms - metabolism, Protein Isoforms - secretion, Proteolysis, Proteome - metabolism, Scientific imaging, Signal Transduction, Toll-like receptors, Toll-Like Receptors - genetics, Toll-Like Receptors - metabolism, Transcriptome

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