Introduction

The heat shock protein (Hsp) 70 family is a collection of evolutionarily conserved, ubiquitous proteins that are either constitutively expressed and/or stress induced and which are nominally defined by their molecular weight (Hsp70, Hsc73, BiP (binding immunoglobulin protein, or glucose regulated protein (grp) 78)). Historically, these proteins have been perceived to function as intracellular molecular chaperones that ensure the correct folding of nascent proteins and are involved in the translocation of proteins and assist in protein degradation through the proteasome [1]. At times of physical or chemical stress, such chaperones are upregulated by the unfolded protein response and provide protection against the accumulation and aggregation of denatured proteins.

In contrast to this long-standing perception, there is now increasing interest in an intercellular signalling role for these proteins and, as a consequence, they have been termed ‘chaperokines’ in light of their cytokine-like qualities [2, 3]. The interaction between heat shock proteins and specific cell surface receptors that signal the release of inflammatory mediators has revealed a link between the innate and adaptive immune response. A wide range of extracellular receptors for human Hsp70 has been identified. These include CD14 [2, 4, 5], Toll-like receptor (TLR) 4, TLR2 [4, 6], CD91 [7, 8] and CD40 [9, 10] on monocytes, and scavenger receptors such as LOX-1 on dendritic cells (DCs) [11]. The role of these receptors is detailed in Chapters 7 and 10.