期刊
PLOS GENETICS
卷 2, 期 11, 页码 1725-1739出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.0020183
关键词
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资金
- NIAID NIH HHS [AI053595, K08 AI053595, R01 AI064332, AI064332] Funding Source: Medline
- NIA NIH HHS [AG024425-01, R56 AG024425, R01 AG024425] Funding Source: Medline
- NIDDK NIH HHS [P30 DK040561-11, P30 DK040561] Funding Source: Medline
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.
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