Role of HSF1 in Infectious Disease

The single heat shock transcription factor (HSF) in lower Metazoans and the heat-activated HSF family member in higher vertebrates, HSF1, not only play a central role in regulating the expression of heat shock protein (HSP) genes in response to stress, but may also play an important role in regulating the host immune response to infection. HSF is modified by pro-inflammatory signaling stimulated by microbial pathogens, pathogen-derived products, and elements of the host acute phase response including fever. In addition to its actions on heat shock protein, HSF can regulate activation of immunoregulatory signaling pathways and regulate expression of several pro-inflammatory factors. Therefore HSF serves as an important functional interface between heat shock and pro-inflammatory signaling pathways that mediate reciprocal regulation of both responses. Severe sepsis and septic shock are serious, often fatal complications of infections, caused by dysregulation of the host immune response. Understanding how the convergence of stress and inflammatory pathways on HSF shape the host response in the infected host provides new insights into disease pathogenesis and new therapeutic targets to modify the course of infectious disease.