Heat shock and genetic activation of HSF-1 enhance immunity to bacteria.
The relationship between fever and microbial infections has been known for a number of years, as well as several key mediators involved in its elicitation. However, the mechanisms by which fever confers protection to infected hosts are less clear. The nematode Caenorhabditis elegans, which has been extensively used in recent years to study microbial infections and innate immune responses, has recently been used to study the effect of increased temperature in immunity. Upon heat shock exposure, nematodes become more resistant to Pseudomonas aeruginosa and the enhanced resistance to the pathogen requires heat shock transcription factor 1 (HSF-1) and a system of small and 90 kDa heat shock proteins (HSPs). Experiments using additional Gram negative and Gram positive pathogens show that HSF-1 is part of a multipathogen defense pathway. In addition, C. elegans innate immunity can be activated enhancing HSF-1 activity by directly overexpressing HSF-1 or by overexpressing DAF-16, which is a forkhead transcription factor that acts upstream HSF-1 in aging and immunity. Blocking the inhibitory signal of the DAF-2 insulin like receptor, which acts upstream DAF-16, also results in an enhanced HSF-1 dependent immunity. In addition, mutations that affect DAF-21, C. elegans homologue of Hsp90 which forms an inhibitory complex with HSF-1, appear to boost immunity by activating the HSF-1 pathway. The role of the HSF-1 pathway in innate immunity and immunosenescence is discussed.
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