An effector Peptide family required for Drosophila toll-mediated immunity.
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.
Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
Alexa W
AW
Clemmons
Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
Scott A
SA
Lindsay
Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
Steven A
SA
Wasserman
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D041221:Candida glabrata / Q000276:immunology / Q000502:physiology; D019295:Computational Biology; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D013293:Enterococcus faecalis / Q000276:immunology / Q000502:physiology; D005670:Fusarium / Q000276:immunology / Q000502:physiology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D053208:Kaplan-Meier Estimate; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D020543:Proteome / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
D023181:Antimicrobial Cationic Peptides; D029721:Drosophila Proteins; D010446:Peptide Fragments; D010455:Peptides; D020033:Protein Isoforms; D020543:Proteome; D051193:Toll-Like Receptors