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Da Costa, C.U. et al. Heat shock protein 60 from Chlamydia pneumoniae elicits an unusual set of inflammatory responses via Toll-like receptor 2 and 4 in vivo. Eur. J. Immunol. 34, 2874-2884

Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
European Journal of Immunology (Impact Factor: 4.03). 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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    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.
    Full-text · Article · Jul 2013 · Journal of Reproductive Immunology
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    • "Results from our study demonstrate a powerful antibody response against HSP60 from C. trachomatis indicating that HSP60 is a strong B cell antigen. Furthermore, chlamydial HSP60 is known to mediate proinflammatory responses through toll-like receptor 2 and 4 (Bulut et al., 2002; Da Costa et al., 2004). This suggests HSP60 as an important chlamydial antigen and inflammatory mediator in the generation of TFI. Figure 2 ROC curves showing the true-positive rate (sensitivity) against the false-positive rate (12specificity) for the different possible cut-offs of the diagnostic analyses based on serum levels of IgG1 and IgG3 antibodies against chlamydial MOMP (A and B), HSP60 from C. trachomatis (C and D), S. enterica Enteritidis HSP60 (E), C. jejuni HSP60 (F) and human HSP60 (G and H) in patients with TFI and individuals with normal fallopian tubes (control group 1). "
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    ABSTRACT: Serum antibodies against major outer membrane protein (MOMP) and heat shock protein 60 (HSP60) from Chlamydia trachomatis are correlated with sequelae following infection. Since bacterial and human HSP60 share considerable sequence homology, cross-reactivity to human HSP60 is suggested as being involved in tubal factor infertility (TFI). The aim was to investigate whether antibodies to human HSP60 are associated with TFI, and to evaluate antibody testing in TFI diagnosis. Serum levels of antibodies against chlamydial MOMP and HSP60 from C. trachomatis, Salmonella enterica Enteritidis, Campylobacter jejuni and human HSP60 were analysed by enzyme-linked immunosorbent assay in three groups of infertile women: women with TFI (n = 70), controls with normal fallopian tubes (control group 1, n = 92) and a subgroup of women with normal fallopian tubes and sero-positive for either chlamydial MOMP or chlamydial HSP60 (control group 2, n = 28). Serum levels of immunoglobulin (Ig)G1 and IgG3 antibodies against MOMP and HSP60 from C. trachomatis were elevated in patients with TFI compared with non-TFI individuals (group 1; P < 0.001), while levels of IgG3 against MOMP and IgG1 against HSP60 were higher in the TFI group compared with control group 2 (P = 0.04 and P = 0.03, respectively). Levels of antibodies against human HSP60 did not differ between groups. Our findings confirm an association between TFI and antibodies to MOMP and HSP60 from C. trachomatis, suggesting antibody testing as a supplement in TFI diagnosis. No connection was observed between TFI and antibodies to human HSP60, pointing to an infectious rather than an autoimmune inflammation as the cause of TFI.
    Preview · Article · Jun 2011 · Human Reproduction
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    • "As such, the atherosclerotic plaque is likely to contain many endogenous ligands (Table 1). For example, HSPs induce the production of proinflammatory cytokines in a TLR2- and TLR4-dependent pathway [105, 106]. Degradation products of extracellular matrix macromolecules are generated during tissue injury, or remodelling, and have been found to function as TLR ligands. "
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    ABSTRACT: Inflammation drives atherosclerosis. Both immune and resident vascular cell types are involved in the development of atherosclerotic lesions. The phenotype and function of these cells are key in determining the development of lesions. Toll-like receptors are the most characterised innate immune receptors and are responsible for the recognition of exogenous conserved motifs on pathogens, and, potentially, some endogenous molecules. Both endogenous and exogenous TLR agonists may be present in atherosclerotic plaques. Engagement of toll-like receptors on immune and resident vascular cells can affect atherogenesis as signalling downstream of these receptors can elicit proinflammatory cytokine release, lipid uptake, and foam cell formation and activate cells of the adaptive immune system. In this paper, we will describe the expression of TLRs on immune and resident vascular cells, highlight the TLR ligands that may act through TLRs on these cells, and discuss the consequences of TLR activation in atherosclerosis.
    Full-text · Article · Jun 2010 · Mediators of Inflammation
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