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Infect Immun. 2011 Jan;79(1):177-84. doi: 10.1128/IAI.00742-09. Epub 2010 Oct 18.

Heat shock factor 1 protects mice from rapid death during Listeria monocytogenes infection by regulating expression of tumor necrosis factor alpha during fever.

Author information

1
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, 800 Rose Street-MS401, Lexington, KY 40536, USA.

Abstract

Heat shock factor 1 (HSF1) is a stress-induced transcription factor that promotes expression of genes that protect mammalian cells from the lethal effects of severely elevated temperatures (>42°C). However, we recently showed that HSF1 is activated at a lower temperature (39.5°C) in T cells, suggesting that HSF1 may be important for preserving T cell function during pathogen-induced fever responses. To test this, we examined the role of HSF1 in clearance of Listeria monocytogenes, an intracellular bacterial pathogen that elicits a strong CD8(+) T cell response in mice. Using temperature transponder microchips, we showed that the core body temperature increased approximately 2°C in L. monocytogenes-infected mice and that the fever response was maintained for at least 24 h. HSF1-deficient mice cleared a low-dose infection with slightly slower kinetics than did HSF1(+/+) littermate controls but were significantly more susceptible to challenges with higher doses of bacteria. Surprisingly, HSF1-deficient mice did not show a defect in CD8(+) T cell responses following sublethal infection. However, when HSF1-deficient mice were challenged with high doses of L. monocytogenes, increased levels of serum tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) compared to those of littermate control mice were observed, and rapid death of the animals occurred within 48 to 60 h of infection. Neutralization of TNF-α enhanced the survival of HSF1-deficient mice. These results suggest that HSF1 is needed to prevent the overproduction of proinflammatory cytokines and subsequent death due to septic shock that can result following high-dose challenge with bacterial pathogens.

PMID:
20956571
PMCID:
PMC3019880
DOI:
10.1128/IAI.00742-09
[Indexed for MEDLINE]
Free PMC Article

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