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Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity
Varsha Singh, and
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710
Edited by Frederick M. Ausubel, Harvard Medical School, Boston, MA, and approved July 11, 2006
Received for publication May 16, 2006.
Innate immunity comprises physical barriers, pattern-recognitionreceptors, antimicrobial substances, phagocytosis, and fever.Here we report that increased temperature results in the activationof a conserved pathway involving the heat-shock (HS) transcriptionfactor (HSF)-1 that enhances immunity in the invertebrate Caenorhabditiselegans. The HSF-1 defense response is independent of the p38MAPK/PMK-1 pathway and requires a system of chaperones includingsmall and 90-kDa inducible HS proteins. In addition, HSF-1 isneeded for the effects of the DAF-2 insulin-like pathway indefense to pathogens, indicating that interacting pathways controlstress response, aging, and immunity. The results also showthat HSF-1 is required for C. elegans immunity against Pseudomonasaeruginosa, Salmonella enterica, Yersinia pestis, and Enterococcusfaecalis, indicating that HSF-1 is part of a multipathogen defensepathway. Considering that several coinducers of HSF-1 are currentlyin clinical trials, this work opens the possibility that activationof HSF-1 could be used to boost immunity to treat infectiousdiseases and immunodeficiencies.