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Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13092-7. Epub 2006 Aug 17.

Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity.

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  • 1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.

Abstract

Innate immunity comprises physical barriers, pattern-recognition receptors, antimicrobial substances, phagocytosis, and fever. Here we report that increased temperature results in the activation of a conserved pathway involving the heat-shock (HS) transcription factor (HSF)-1 that enhances immunity in the invertebrate Caenorhabditis elegans. The HSF-1 defense response is independent of the p38 MAPK/PMK-1 pathway and requires a system of chaperones including small and 90-kDa inducible HS proteins. In addition, HSF-1 is needed for the effects of the DAF-2 insulin-like pathway in defense to pathogens, indicating that interacting pathways control stress response, aging, and immunity. The results also show that HSF-1 is required for C. elegans immunity against Pseudomonas aeruginosa, Salmonella enterica, Yersinia pestis, and Enterococcus faecalis, indicating that HSF-1 is part of a multipathogen defense pathway. Considering that several coinducers of HSF-1 are currently in clinical trials, this work opens the possibility that activation of HSF-1 could be used to boost immunity to treat infectious diseases and immunodeficiencies.

PMID:
16916933
[PubMed - indexed for MEDLINE]
PMCID:
PMC1559758
Free PMC Article
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