Membrane-Expressed and Extracellular Stress Proteins in Infectious Disease

Abstract

This chapter focuses on the dichotomous effects of eukaryotic and microbial heat shock proteins (HSPs) with molecular weights of 60, 70, and 90 kDa on the host’s immune system. It has previously been shown that membrane-bound and extracellular heat shock proteins elicit potent anti-cancer immune responses. Herein are discussed the immunostimulatory and immunosuppressive properties of heat shock proteins in bacterial and viral infections. Binding of peptide-free heat shock proteins to surface receptors on antigen presenting cells (APCs) induces the secretion of pro-inflammatory cytokines and thus might result in a non-specific stimulation of the cellular immune system. Moreover, soluble as well as cell membrane-bound heat shock proteins have the capacity to directly activate the cytolytic activity of the innate and adaptive immune system against microbial infected cells. However, depending on the microenvironment, heat shock proteins also mediate anti-inflammatory functions. In summary, depending on their mode of induction, extracellular or membrane localization, cellular origin (eukaryote/prokaryote), peptide loading status, intracellular ADP/ATP content, concentration, and route of application, heat shock proteins either exert immune activation as `danger’ signals or mediate protection against infectious diseases.