Synergistic and differential modulation of immune responses by Hsp60 and lipopolysaccharide.
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.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractActivation 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.
CitationSynergistic and differential modulation of immune responses by Hsp60 and lipopolysaccharide. 2007, 282 (7):4669-80 J. Biol. Chem.
AffiliationDepartment of Immunology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany. firstname.lastname@example.org
The following license files are associated with this item:
- 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
- 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
- Toll-like receptor-dependent activation of antigen-presenting cells affects adaptive immunity to Helicobacter pylori.
- Authors: Rad R, Brenner L, Krug A, Voland P, Mages J, Lang R, Schwendy S, Reindl W, Dossumbekova A, Ballhorn W, Wagner H, Schmid RM, Bauer S, Prinz C
- Issue date: 2007 Jul
- Lectin-like oxidized low-density lipoprotein receptor-1 delivers heat shock protein 60-fused antigen into the MHC class I presentation pathway.
- Authors: Xie J, Zhu H, Guo L, Ruan Y, Wang L, Sun L, Zhou L, Wu W, Yun X, Shen A, Gu J
- Issue date: 2010 Aug 15
- Activation of murine macrophages by Neisseria meningitidis and IFN-gamma in vitro: distinct roles of class A scavenger and Toll-like pattern recognition receptors in selective modulation of surface phenotype.
- Authors: Mukhopadhyay S, Peiser L, Gordon S
- Issue date: 2004 Sep