Chaperonins in disease: mechanisms, models, and treatments

Abstract

Chaperonins are oligomeric proteins that assist in the folding of nascent or denatured proteins. Bacterial chaperonins are strongly immunogenic and can cause tissue pathology. They have been implicated in infection, autoimmune disease, and idiopathic or multifactorial diseases, such as arthritis and atherosclerosis. Chaperonin 60 proteins are also involved in prion diseases. In the past few years, much progress has been made in unravelling the involvement of various bacterial and mammalian chaperonin 60 (Cpn 60 or hsp 60) proteins in such diseases, and in proposing mechanisms for their biological actions, although we are still some way from a full understanding of chaperonin action that might lead to immunotherapeutic approaches. This review focuses on the current knowledge of the roles of Cpn 60 in the pathology of infectious and immune diseases, and discusses models for the actions of this molecule. Some potential therapeutic strategies will also be reviewed.

Figure 1

Effects of bacterial chaperonin 60 (Cpn 60) on eukaryotic cells. Bacterial Cpn 60 induces vascular endothelial cells to secrete intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin. These play a role in attracting macrophages and lymphocytes to the site of infection. Cpn 60 binds directly to macrophages via pathogen recognition receptors (PPRs), such as the Toll-like receptors, and induces the production and secretion of pro-inflammatory cytokines, thus further enhancing cellular migration to the site of infection. Antigen presenting cells can also present Cpn 60 peptides to T cells on the major histocompatibility complex (MHC), thus inducing the proliferation of T and B cells and initiating a protective immune response. TCR, T cell receptor.