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PNAS 103 (35): 13092-13097

Copyright © 2006 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / CELL BIOLOGY

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

Varsha Singh, and Alejandro Aballay*

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.

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.

Key Words: heat-shock protein • innate immunity • MAPK • infection • pathogen

Author contributions: A.A. and V.S. designed research; V.S. performed research; A.A. and V.S. analyzed data; and A.A. and V.S. wrote the paper.

Conflict of interest statement: No conflicts declared.

This paper was submitted directly (Track II) to the PNAS office.

*To whom correspondence should be addressed at: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Box 3054 DUMC, Durham, NC 27710. E-mail: a.aballay{at}duke.edu

© 2006 by The National Academy of Sciences of the USA

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