GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:17164250

From GONUTS
Jump to: navigation, search
Citation

Osterloh, A, Kalinke, U, Weiss, S, Fleischer, B and Breloer, M (2007) Synergistic and differential modulation of immune responses by Hsp60 and lipopolysaccharide. J. Biol. Chem. 282:4669-80

Abstract

Activation of professional antigen-presenting cells (APC) is a crucial step in the initiation of an efficient immune response. In this study we show that Hsp60 mediates immune stimulation by different mechanisms, dependent and independent of lipopolysaccharide (LPS). We have demonstrated earlier that both, Hsp60 and LPS, increase antigen-specific interferon (IFN) gamma release in T cells. Here we show that in contrast to LPS Hsp60 induces IFNalpha production in professional APC. Neutralization of IFNalpha as well as the absence of functional IFNalphabeta receptor on APC and T cells interfered with Hsp60-mediated IFNgamma secretion in antigen-dependent T cell activation, strongly suggesting that IFNalpha represents one factor contributing to Hsp60-specific immune stimulation. On the other hand, we show that Hsp60 bound to the cell surface of APC colocalizes with the LPS co-receptor CD14 and LPS binding sites. Hsp60 specifically binds bacterial LPS and both molecules synergistically enhanced IL-12p40 production in APC and IFNgamma release in antigen-dependent T cell activation. This effect was Hsp60-specific and dependent on LPS-binding by Hsp60. Furthermore, we show that Hsp60 exclusively binds to macrophages and DC but not to T or B lymphocytes and that both, T cell stimulation by Hsp60 as well as Hsp60/LPS complexes, strictly depends on the presence of professional APC and is not mediated by B cells. Taken together, our data support an extension of the concept of Hsp60 as an endogenous danger signal: besides its function as a classical danger signal indicating unplanned tissue destruction to the innate immune system, in the incident of bacterial infection extracellular Hsp60 may bind LPS and facilitate microbe recognition by lowering the threshold of pathogen-associated molecular pattern (PAMP) detection and enhancing Toll-like receptor (TLR) signaling.

Links

PubMed Online version:10.1074/jbc.M608666200

Keywords

Animals; Antigen Presentation/genetics; Antigen Presentation/immunology; Antigens, CD14/immunology; COS Cells; Cercopithecus aethiops; Chaperonin 60/immunology; Cytokines/genetics; Cytokines/immunology; Dendritic Cells/cytology; Dendritic Cells/immunology; Immunity, Innate/genetics; Leukocytes/cytology; Leukocytes/immunology; Lipopolysaccharides/immunology; Lymphocyte Activation/immunology; Mice; Mice, Inbred BALB C; Mice, Knockout; Protein Binding/genetics; Protein Binding/immunology; Receptor, Interferon alpha-beta/genetics; Receptor, Interferon alpha-beta/immunology; Signal Transduction/genetics; Signal Transduction/immunology; Toll-Like Receptors/genetics; Toll-Like Receptors/immunology

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

See Help:References for how to manage references in GONUTS.