Synergistic and differential modulation of immune responses by Hsp60 and lipopolysaccharide.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Issue Date
2007-02-16
Metadata
Show full item recordAbstract
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.Citation
Synergistic and differential modulation of immune responses by Hsp60 and lipopolysaccharide. 2007, 282 (7):4669-80 J. Biol. Chem.Affiliation
Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany. osterloh@bni.uni-hamburg.dePubMed ID
17164250Type
ArticleLanguage
enISSN
0021-9258ae974a485f413a2113503eed53cd6c53
10.1074/jbc.M608666200
Scopus Count
The following license files are associated with this item:
Related articles
- Hsp60-mediated T cell stimulation is independent of TLR4 and IL-12.
- Authors: Osterloh A, Veit A, Gessner A, Fleischer B, Breloer M
- Issue date: 2008 Mar
- Human heat shock protein 60 induces maturation of dendritic cells versus a Th1-promoting phenotype.
- Authors: Flohé SB, Brüggemann J, Lendemans S, Nikulina M, Meierhoff G, Flohé S, Kolb H
- Issue date: 2003 Mar 1
- Macrophages as main inducers of IFN-gamma in T cells following administration of human and mouse heat shock protein 60.
- Authors: Breloer M, Moré SH, Osterloh A, Stelter F, Jack RS, Bonin Av Av
- Issue date: 2002 Nov
- Eukaryotic heat shock proteins as molecular links in innate and adaptive immune responses: Hsp60-mediated activation of cytotoxic T cells.
- Authors: Moré SH, Breloer M, von Bonin A
- Issue date: 2001 Sep
- Lipopolysaccharide-free heat shock protein 60 activates T cells.
- Authors: Osterloh A, Meier-Stiegen F, Veit A, Fleischer B, von Bonin A, Breloer M
- Issue date: 2004 Nov 12