Trends in Immunology
Volume 32, Issue 2, February 2011, Pages 89-95
Journal home page for Trends in Immunology

Review
The HSP60 immune system network

https://doi.org/10.1016/j.it.2010.11.001Get rights and content

Heat shock proteins (HSPs) were initially discovered as participants in the cellular response to stress. It is now clear, however, that self and microbial HSPs also play an important role in the control of the immune response. Here, we focus on HSP60 and its interactions with both the innate and adaptive immune system in mammals. We also consider that circulating HSP60 and the quantities and specificities of serum antibodies to HSP60 provide a biomarker to monitor the immune status of the individual. Thus, the dual role of HSP60 as an immune modulator and a biomarker, provides an opportunity to modulate immunity for therapeutic purposes, and to monitor the immune response in health and disease.

Section snippets

Nodes and links in complex networks

Living systems, like other complex systems, can be characterized by their networks of interactions [1]. The immune system is a telling example of a network: the interactions that occur between subsets of innate and adaptive immune cells are necessary to initiate a functional and specific immune response. A standard approach for mapping these interactions is to formulate the architecture of interaction networks using a terminology of nodes and links. The nodes are the entities that interact, and

Intercellular immune functions of HSP60

The presence of soluble HSP60 in the blood coincides with various inflammatory conditions (reviewed in 13, 14). It has been suggested that HSP60 is secreted from cells in detergent-soluble lipid vesicles [18] or exosomes 19, 20. The release of intact or fragmented HSP60 from damaged or dead cells is also a possibility [21]. Although the exact mechanism(s) by which HSP60 is secreted into the extracellular medium is not understood, it is clear that extracellular HSP60 is a link between body

Is HSP60 pro-inflammatory or anti-inflammatory; a danger signal or a resolving signal?

Figure 1 summarizes our current knowledge of the HSP60 network: HSP60 is both an antigen, via the TCR and the BCR, and an innate link to adaptive immunity via activation of TLR4 and TLR2. HSP60 is both a pro-inflammatory signal, via monocytes, B cells and effector T cells, and an anti-inflammatory signal, via B cells, Tregs, and anti-ergotypic T cells. The integrated effects of HSP60 on the immune response depend on the concentration, the particular HSP60 epitope (bacterial or self), and the

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