Abstract
Recent studies of heat shock protein-mediated modulation of the inflammatory and immune responses suggest its involvement in host responses to infection. In addition, during infection, the mammalian host is faced with the interaction of the heat shock responses of two competing organisms. Indeed, both mammalian and pathogenic heat shock proteins bind to host cells where they can signal danger, mediate inflammation and influence immune cell function. These overlapping repertoires of stress proteins may thus participate in determining the outcome of pathogenic infections by their abilities to take part in, work to prevent, or resolve infection. In this account, we have examined the role of heat shock proteins largely from the point of view of the mammalian host during the infection by non-viral microorganisms. When assessing the role of heat shock proteins in infection, a number of issues must be unraveled. The first is the relative roles of intracellular and extracellular mammalian heat shock proteins in pro- or anti-inflammatory processes. It is thus apparent that the intracellular heat shock proteins, heat shock transcription factor1 (HSF1) and the heat shock response (HSR) influence the infection of mammals by pathogenic organisms. The HSR and intracellular heat shock proteins protect against severe sepsis and fever as demonstrated in experiments using Hsp70 and HSF1 knockout mice. However, in addition, heat shock protein in the extracellular spaces may be involved in earlier phases of infection, in processes such as in complement activation, microorganism engulfment by phagocytes, cytokine secretion and immune responses to pathogens.
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We acknowledge the support of the Department of Radiation Oncology at BIDMC. These studies were also supported by NIH grants 5RO1CA047407 and 3RO1CA094397 (SKC).
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Calderwood, S.K., Murshid, A., Zhu, B., Mambula, S.S. (2009). Role of Host Molecular Chaperones in Responses to Bacterial Infection and Endotoxin Exposure. In: Pockley, A., Calderwood, S., Santoro, M. (eds) Prokaryotic and Eukaryotic Heat Shock Proteins in Infectious Disease. Heat Shock Proteins, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2976-8_5
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