Heat shock protein 60 from Chlamydia pneumoniae elicits an unusual set of inflammatory responses via Toll-like receptor 2 and 4 in vivo

Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
European Journal of Immunology (Impact Factor: 4.52). 11/2004; 34(10):2874-84. DOI: 10.1002/eji.200425101
Source: PubMed

ABSTRACT Heat shock protein 60 (HSP60) from Chlamydia pneumoniae was described to trigger in vitro inflammatory and cytokine responses including TNF and IL-12p40. Although it can be found in atherosclerotic plaques of patients, the stimulatory potential of chlamydial and other HSP60 in vivo is unclear. We now report that chlamydial HSP60 fails to induce TNF expression in vivo, and significant serum levels of IL-12p40 are only found upon intraperitoneal injection of high doses of HSP60 or after intravenous application. Upon purification of chlamydial HSP60 with polymyxin B-agarose columns, its ability to induce TNF secretion in vitro is much reduced. However, purified chlamydial HSP60 causes increased serum levels of the CXC chemokines KC and MIP2 in vivo, as well as a strong accumulation of polymorphonuclear neutrophils (PMN) in the peritoneal cavity upon intraperitoneal challenge. With respect to PMN accumulation, chlamydial HSP60 is more potent than endotoxin or the CpG oligonucleotide 1668. The responses observed are completely abolished in Toll-like receptor (TLR)2/4-double-deficient mice, while single-deficient mice respond almost normally. Furthermore, KC induction and PMN accumulation are largely dependent on MyD88. In conclusion, HSP60 from C. pneumoniae triggers inflammatory responses in vivo that differ from responses induced by endotoxin or CpG oligonucleotides and are dependent on TLR2 and 4.

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    • "Identifying chlamydial antigens involved in MyD88/TLR dependent recognition and subsequent TLR-driven immune pathology is a major issue in Chlamydia research (Joyee and Yang, 2008). Several studies have shown that chlamydial LPS and HSP60 are associated with TLR2 and TLR4 recognition by monocytes or dendritic cells (Vabulas et al., 2001; Heine et al., 2003; da Costa et al., 2004). Moreover, macrophage infectivity potentiator (Mip) has been associated with TLR2 recognition (Bas et al., 2008). "
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    • "Moreover, additional studies indicate that not only one but several other subtypes of TLR might be crucial for host cell activation via Cp. Studies concerning dendritic cells were able to depict a role of both TLR2/4 in cHSP60-dependent inflammatory processes (Da Costa et al., 2004). However, even receptors other than TLR2/4, for example receptors of the Nod family seem to be involved in host cell activation as cells lacking these receptor subtypes could be activated sufficiently through Cp (Krüll et al., 2005; Opitz et al., 2005). "
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