Editors' ChoiceImmunology

Worms with Fevers

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Science's STKE  05 Sep 2006:
Vol. 2006, Issue 351, pp. tw304
DOI: 10.1126/stke.3512006tw304

Ever wondered whether taking medicine to reduce a fever might inhibit a protective response of the body to infection? New evidence for such a possibility is presented by Singh and Aballay, who report studies of the effects of increased temperature on immunity of the nematode C. elegans to bacterial infections. Worms don't have fevers, of course, but such poikilotherms are known to respond to infection by migrating toward a warmer environment. Exposure of C. elegans to heat shock (incubation at 32°C for 2 hours) increased resistance and delayed the death of animals exposed to the human pathogen Pseudomonas aerugninosa. The p38 MAPK (mitogen-activated protein kinase) pathway was not required for this effect, but the heat-shock transcription factor HSF-1 was. No protective effect of heat shock was evident in animals treated with hsf-1 RNAi, and overexpression of HSF-1 made animals more resistant to infection. Genes encoding the heat-shock protein (HSP) chaperones are controlled by HSF-1, and RNAi to HSP-encoding genes increased susceptibility of the worms to infection. The forkhead transcription factor DAF-16 regulates genes that influence longevity as well as stress responses and is positively regulated by heat shock. Animals expressing additional gene copies of daf-16 or with mutations in daf-2 (a gene encoding an insulin-like negative regulator of DAF-16) showed increased resistance to pathogens that was reduced in animals in which function of HSF-1 was inhibited by RNAi. Thus, HSF-1 appears to be part of a protective heat-induced response to infection. The authors propose that therapeutic agents aimed at activation of the HSF-1 pathway (without the additional dangerous effects of high fevers) might be effective for treatment of bacterial infections.

V. Singh, A. Aballay, Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. Proc. Natl. Acad. Sci. U.S.A. 103, 13092-13097 (2006). [Abstract] [Full Text]

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