Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity.
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.
Singh
Varsha
V
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Aballay
Alejandro
A
D000818:Animals; D017173:Caenorhabditis elegans / Q000276:immunology* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D006094:Gram-Positive Bacteria / Q000502:physiology; D006979:Hyperthermia, Induced; D007109:Immunity; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000502:physiology; D011972:Receptor, Insulin / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D018832:Molecular Chaperones; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C474710:heat shock factor-1, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D048670:MAP Kinase Kinase 4