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Apr, 2015;11 (4): e1004876.

An effector Peptide family required for Drosophila toll-mediated immunity.

Alexa W Clemmons, Scott A Lindsay, Steven A Wasserman
Author Information
  1. Alexa W Clemmons: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
  2. Scott A Lindsay: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
  3. Steven A Wasserman: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
PMID: 25915418 DOI: 10.1371/journal.ppat.1004876

Abstract

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.

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Grants

  1. R01 GM050545/NIGMS NIH HHS
  2. T32 GM008666/NIGMS NIH HHS
  3. R01GM050545-16/NIGMS NIH HHS

MeSH Term

Animals
Antimicrobial Cationic Peptides
Candida glabrata
Computational Biology
Drosophila Proteins
Drosophila melanogaster
Enterococcus faecalis
Fusarium
Gene Deletion
Gene Expression Regulation
Host-Pathogen Interactions
Immunity, Innate
Kaplan-Meier Estimate
Male
Peptide Fragments
Peptides
Protein Isoforms
Proteolysis
Proteome
Signal Transduction
Toll-Like Receptors
Transcriptome

Chemicals

Antimicrobial Cationic Peptides
Drosophila Proteins
Peptide Fragments
Peptides
Protein Isoforms
Proteome
Toll-Like Receptors
Journal Article Research Support, N.I.H., Extramural
Article has an altmetric score of 8

Word Cloud

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