Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

PNAS 103 (35): 13092-13097

Copyright © 2006 by the National Academy of Sciences.


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}

© 2006 by The National Academy of Sciences of the USA

The Conserved PBAF Nucleosome-Remodeling Complex Mediates the Response to Stress in Caenorhabditis elegans.
A. Kuzmanov, E. I. Karina, N. V. Kirienko, and D. S. Fay (2014)
Mol. Cell. Biol. 34, 1121-1135
   Abstract »    Full Text »    PDF »
A Neuronal GPCR is Critical for the Induction of the Heat Shock Response in the Nematode C. elegans.
M. Maman, F. Carvalhal Marques, Y. Volovik, T. Dubnikov, M. Bejerano-Sagie, and E. Cohen (2013)
J. Neurosci. 33, 6102-6111
   Abstract »    Full Text »    PDF »
Effect of Caenorhabditis elegans age and genotype on horizontal gene transfer in intestinal bacteria.
C. Portal-Celhay, K. Nehrke, and M. J. Blaser (2013)
FASEB J 27, 760-768
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Stress Pathway Required for Immune Homeostasis Is Neurally Controlled by Arrestin-1.
V. Singh and A. Aballay (2012)
J. Biol. Chem. 287, 33191-33197
   Abstract »    Full Text »    PDF »
Heat Shock Factor 1 Protects Mice from Rapid Death during Listeria monocytogenes Infection by Regulating Expression of Tumor Necrosis Factor Alpha during Fever.
P. Murapa, M. R. Ward, S. K. Gandhapudi, J. G. Woodward, and S. E. F. D'Orazio (2011)
Infect. Immun. 79, 177-184
   Abstract »    Full Text »    PDF »
SLR-2 and JMJC-1 regulate an evolutionarily conserved stress-response network.
N. V. Kirienko and D. S. Fay (2010)
EMBO J. 29, 727-739
   Abstract »    Full Text »    PDF »
bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans.
K. A. Estes, T. L. Dunbar, J. R. Powell, F. M. Ausubel, and E. R. Troemel (2010)
PNAS 107, 2153-2158
   Abstract »    Full Text »    PDF »
Regulation of DAF-16-mediated Innate Immunity in Caenorhabditis elegans.
V. Singh and A. Aballay (2009)
J. Biol. Chem. 284, 35580-35587
   Abstract »    Full Text »    PDF »
Autophagy genes protect against Salmonella typhimurium infection and mediate insulin signaling-regulated pathogen resistance.
K. Jia, C. Thomas, M. Akbar, Q. Sun, B. Adams-Huet, C. Gilpin, and B. Levine (2009)
PNAS 106, 14564-14569
   Abstract »    Full Text »    PDF »
Inhibition of a eukaryotic initiation factor (eIF2B{delta}/F11A3.2) during adulthood extends lifespan in Caenorhabditis elegans.
D. Tohyama, A. Yamaguchi, and T. Yamashita (2008)
FASEB J 22, 4327-4337
   Abstract »    Full Text »    PDF »
Studying host-pathogen interactions and innate immunity in Caenorhabditis elegans.
D. Kim (2008)
Dis. Model. Mech. 1, 205-208
   Abstract »    Full Text »    PDF »
DAF-16-Dependent Suppression of Immunity During Reproduction in Caenorhabditis elegans.
S. Miyata, J. Begun, E. R. Troemel, and F. M. Ausubel (2008)
Genetics 178, 903-918
   Abstract »    Full Text »    PDF »
Insulin Signaling and the Heat Shock Response Modulate Protein Homeostasis in the Caenorhabditis elegans Intestine during Infection.
A. Mohri-Shiomi and D. A. Garsin (2008)
J. Biol. Chem. 283, 194-201
   Abstract »    Full Text »    PDF »
A conserved Toll-like receptor is required for Caenorhabditis elegans innate immunity.
J. L. Tenor and A. Aballay (2008)
EMBO Rep. 9, 103-109
   Abstract »    Full Text »    PDF »
Oxidative Stress Enzymes Are Required for DAF-16-Mediated Immunity Due to Generation of Reactive Oxygen Species by Caenorhabditis elegans.
V. Chavez, A. Mohri-Shiomi, A. Maadani, L. A. Vega, and D. A. Garsin (2007)
Genetics 176, 1567-1577
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882