Identification of innate immunity genes and pathways using a comparative genomics approach.
To reveal regulators of innate immunity, we used RNAi assays to monitor the immune response when genes are inhibited in Caenorhabditis elegans and mouse macrophages. Genes that altered innate immune responsiveness in C. elegans were validated in murine macrophages, resulting in the discovery of 11 genes that regulate the innate immune response in both systems and the subsequent identification of a protein interaction network with a conserved role in innate immunity regulation. We confirmed the role of four of these 11 genes in antimicrobial gene regulation using available mutants in C. elegans. Several of these genes (acy-1, tub-2, and tbc-1) also regulate susceptibility to the pathogen Pseudomonas aeruginosa. These genes may prove critical to understanding host defense and represent potential therapeutic targets for infectious and immunological diseases.
Alper
Scott
S
Laboratory of Environmental Lung Disease, National Heart Lung and Blood Institute, National Institutes of Health, 111 TW Alexander Drive, Durham, NC 27709, USA. alpers@nhlbi.nih.gov
Laws
Rebecca
R
Lackford
Brad
B
Boyd
Windy A
WA
Dunlap
Paul
P
Freedman
Jonathan H
JH
Schwartz
David A
DA
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002875:Chromosomes / Q000235:genetics; D005786:Gene Expression Regulation; D023281:Genomics / Q000379:methods*; D007113:Immunity, Innate / Q000235:genetics*; D051379:Mice; D009154:Mutation / Q000235:genetics; D025941:Protein Interaction Mapping; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
D029742:Caenorhabditis elegans Proteins; D011993:Recombinant Fusion Proteins