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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.

Pubmed ID: 18463287

Authors

  • Alper S
  • Laws R
  • Lackford B
  • Boyd WA
  • Dunlap P
  • Freedman JH
  • Schwartz DA

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

May 13, 2008

Associated Grants

  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Chromosomes
  • Gene Expression Regulation
  • Genomics
  • Immunity, Innate
  • Mice
  • Mutation
  • Protein Interaction Mapping
  • RNA Interference
  • Recombinant Fusion Proteins
  • Sequence Homology, Nucleic Acid