Authors: Troemel, Emily R; Chu, Stephanie W; Reinke, Valerie; Lee, Siu Sylvia; Ausubel, Frederick M; Kim, Dennis H
Abstract: The PMK-1 p38 mitogen-activated protein kinase pathway and the DAF-2-DAF-16 insulin signaling pathway control Caenorhabditis elegans intestinal innate immunity. pmk-1 loss-of-function mutants have enhanced sensitivity to pathogens, while daf-2 loss-of-function mutants have enhanced resistance to pathogens that requires upregulation of the DAF-16 transcription factor. We used genetic analysis to show that the pathogen resistance of daf-2 mutants also requires PMK-1. However, genome-wide microarray analysis indicated that there was essentially no overlap between genes positively regulated by PMK-1 and DAF-16, suggesting that they form parallel pathways to promote immunity. We found that PMK-1 controls expression of candidate secreted antimicrobials, including C-type lectins, ShK toxins, and CUB-like genes. Microarray analysis demonstrated that 25% of PMK-1 positively regulated genes are induced by Pseudomonas aeruginosa infection. Using quantitative PCR, we showed that PMK-1 regulates both basal and infection-induced expression of pathogen response genes, while DAF-16 does not. Finally, we used genetic analysis to show that PMK-1 contributes to the enhanced longevity of daf-2 mutants. We propose that the PMK-1 pathway is a specific, indispensable immunity pathway that mediates expression of secreted immune response genes, while the DAF-2-DAF-16 pathway appears to regulate immunity as part of a more general stress response. The contribution of the PMK-1 pathway to the enhanced lifespan of daf-2 mutants suggests that innate immunity is an important determinant of longevity.
Keywords: Animals; Bacterial Infections; Bacterial Toxins/pharmacology; Caenorhabditis elegans/drug effects/*enzymology/microbiology/*physiology; Caenorhabditis elegans Proteins/*metabolism; Genes, Helminth; Immunity/*genetics; Longevity/drug effects/genetics/*immunology/physiology; Mitogen-Activated Protein Kinases/*metabolism; Models, Immunological; Mutation/genetics; Pseudomonas aeruginosa/pathogenicity; Receptor, Insulin/metabolism; Transcription Factors/metabolism; Transcription, Genetic/drug effects; Up-Regulation/drug effects/*genetics; p38 Mitogen-Activated Protein Kinases/*metabolism|
Journal: PLoS Genet Volume: 2 Issue: 11 Pages: e183 Date: Nov. 14, 2006 PMID: 17096597 |
Troemel, Emily R, Chu, Stephanie W, Reinke, Valerie, Lee, Siu Sylvia, Ausubel, Frederick M, Kim, Dennis H (2006) p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet 2: e183.
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