Article

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.

0 Followers
 · 
94 Views
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chlamydia trachomatis (CT) is the most prevalent cause of sexually transmitted diseases. Although the prevalence of chlamydial infection is similar in men and women, current research and screening are still focused on women, who develop the most severe complications, leaving the study of male genital tract (MGT) infection underrated. Herein, we reviewed the literature on genital CT infection with special focus on the MGT. Data indicate that CT certainly infects different parts of the MGT such as the urethra, seminal vesicles, prostate, epididymis and testis. However, whether or not CT infection has detrimental effects on male fertility is still controversial. The most important features of CT infection are its chronic nature and the presence of a mild inflammation that remains subclinical in most individuals. Chlamydia antigens and pathogen recognition receptors (PRR), expressed on epithelial cells and immune cells from the MGT, have been studied in the last years. Toll-like receptor (TLR) expression has been observed in the testis, epididymis, prostate and vas deferens. It has been demonstrated that recognition of chlamydial antigens is associated with TLR2, TLR4, and possibly, other PRRs. CT recognition by PRRs induces a local production of cytokines/chemokines, which, in turn, provoke chronic inflammation that might evolve in the onset of an autoimmune process in genetically susceptible individuals. Understanding local immune response along the MGT, as well as the crosstalk between resident leukocytes, epithelial, and stromal cells, would be crucial in inducing a protective immunity, thus adding to the design of new therapeutic approaches to a Chlamydia vaccine.
    Journal of Reproductive Immunology 07/2013; 100(1). DOI:10.1016/j.jri.2013.05.002 · 2.37 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Since its description in 1986, Chlamydia pneumoniae has remained one of the most enigmatic pathogens. This intracellular bacterium is highly seroprevalent, but rarely recovered from cell culture, it can genetically switch between a proliferative and a nonreplicative state and has been linked to a vast number of chronic diseases, most notably to atherosclerosis, as it can be found in the plaques. It has become quite clear that persistent bacteria in atherosclerotic lesions cannot be eradicated by currently available antibiotic treatments and that attempts to do so without a better understanding of the pathobiology of chlamydial persistence are futile. However, there is growing knowledge on how vascular chlamydial infection may lead to the pathological reprogramming of the host cell signaling pathways. Chlamydia pneumoniae is now well known to induce, at least in vitro, the two pathogenetic main events that define atherosclerosis: angiogenesis and inflammation. In vivo a contribution of chlamydial infection to the progression of atherosclerosis remains unproven. This minireview provides a brief overview on the proproliferative and proinflammatory effects of vascular C. pneumoniae infection and their potential link to atherogenesis.
    FEMS Immunology & Medical Microbiology 04/2009; 55(2):131-9. DOI:10.1111/j.1574-695X.2008.00514.x · 2.55 Impact Factor
  • Source
    • "CXCL8 is released from cells following stimulation with LPS of P. gingivalis and other bacteria and its effects include neutrophil and T-lymphocyte chemotaxis, neutrophil activation and enhanced expression of neutrophil adhesion molecules. CXCL8 was induced following both stimulation by P. gingivalis cells and highly purified P. gingivalis rHtpG, similar to reports that chaperone molecules from a number of bacteria, including H. pylori and C. pneumoniae, induce pro-inflammatory cytokines which may be related to chronic diseases (Da Costa et al., 2004; Lin et al., 2005). CXCL8 is found at significantly high levels in leukocyte tissue infiltrates from gingivitis and chronic periodontitis subjects (Lappin et al., 2003) and evidence supports the notion that these leukocytes are recruited from nearby lymphoid organ/tissue (Kinane et al., 1999; Koulouri et al., 1999), not derived from precursor cells in situ. "
    [Show abstract] [Hide abstract]
    ABSTRACT: CXCL8 (interlukin 8, IL-8) has a diverse spectrum of biological activities including T cell, neutrophil and basophil chemotactic properties. It is produced by a wide variety of cell types and plays a significant role in the initiation of the acute inflammatory response. During inflammation, CXCL8 attracts and activates leukocytes at the site of infection leading to leukocyte infiltration, which can lead to tissue damage. Porphyromonas gingivalis, an aetiological agent of periodontitis, induces production of CXCL8 from several types of cells via its LPS and outer membrane proteins. Bacterial chaperones elicit a strong pro-inflammatory response in cells of the innate immune system. In P. gingivalis the htpG gene codes for the homologue of human Hsp90, a chaperone that associates with transcription factors, hormone receptors and protein kinases, affecting signal transduction pathways. CXCL8 mRNA and CXCL8 protein production was induced in monocytic/human microvascular vein endothelial cells treated with P. gingivalis cells or rHtpG protein. Blocking of receptors CD91 and TLR4 reduced the production of CXCL8 by rHtpG either using receptor-specific antibody or by siRNA silencing. Pre-incubation of P. gingivalis rHtpG preparations with human anti-HtpG significantly inhibited CXCL8 production. A P. gingivalis HtpG disruption mutant also induced less CXCL8 mRNA and protein. These results suggest that P. gingivalis HtpG might be involved in CXCL8-mediated immunopathogenesis.
    Cellular Microbiology 07/2007; 9(6):1611-9. DOI:10.1111/j.1462-5822.2007.00897.x · 4.82 Impact Factor
Show more