Abstract
BackgroundThe magnitude of reproductive morbidity associated with sexually transmitted Chlamydia trachomatis infection is enormous. Association of antibodies to chlamydial heat shock proteins (cHSP) 60 and 10 with various disease sequelae such as infertility or ectopic pregnancy has been reported. Cell-mediated immunity is essential in resolution and in protection to Chlamydia as well as is involved in the immunopathogenesis of chlamydial diseases. To date only peripheral cell mediated immune responses have been evaluated for cHSP60. These studies suggest cHSPs as important factors involved in immunopathological condition associated with infection. Hence study of specific cytokine responses of mononuclear cells from the infectious site to cHSP60 and cHSP10 may elucidate their actual role in the cause of immunopathogenesis and the disease outcome.MethodsFemale patients (n = 368) attending the gynecology out patient department of Safdarjung hospital, New Delhi were enrolled for the study and were clinically characterized into two groups; chlamydia positive fertile women (n = 63) and chlamydia positive infertile women (n = 70). Uninfected healthy women with no infertility problem were enrolled as controls (n = 39). cHSP60 and cHSP10 specific cytokine responses (Interferon (IFN)-gamma, Interleukin (IL)-10, Tumor Necrosis Factor (TNF)-alpha, IL-13 and IL-4) were assessed by ELISA in stimulated cervical mononuclear cell supernatants.ResultscHSP60 and cHSP10 stimulation results in significant increase in IFN-gamma (P = 0.006 and P = 0.04 respectively) and IL-10 levels (P = 0.04) in infertile group as compared to fertile group. A significant cHSP60 specific increase in TNF-alpha levels (P = 0.0008) was observed in infertile group as compared to fertile group. cHSP60 and cHSP10 specific IFN-gamma and IL-10 levels were significantly correlated (P < 0.0001, r = 0.54 and P = 0.004, r = 0.33 respectively) in infertile group.ConclusionOur results suggest that exposure to chlamydial heat shock proteins (cHSP60 and cHSP10) could significantly affect mucosal immune function by increasing the release of IFN-gamma, IL-10 and TNF-alpha by cervical mononuclear cells.
Highlights
The magnitude of reproductive morbidity associated with sexually transmitted Chlamydia trachomatis infection is enormous
Study population Cervical C. trachomatis infection was diagnosed by direct fluorescent assay (DFA)/polymerase chain reaction (PCR) in 174 patients
We found a significant correlation of cHSP60 and cHSP10 IgG antibodies suggesting that co-expression of cHSP60 and cHSP10 occurs at the site of infection too
Summary
The magnitude of reproductive morbidity associated with sexually transmitted Chlamydia trachomatis infection is enormous. To date only peripheral cell mediated immune responses have been evaluated for cHSP60 These studies suggest cHSPs as important factors involved in immunopathological condition associated with infection. The stress response in Chlamydia reticulate bodies is characterized by cHSP60 induction and by reduction in major outer membrane protein and lipopolysaccharide (LPS) levels, as shown in an in vitro model of persistent infection [6,7]. This stress response is believed to interrupt the normal progression of reticulate bodies to infectious elementary bodies, resulting in a longer-term persistent infection. The pathogen's ability to survive stressful environmental conditions and persist in the host is maximized by cHSP60-cHSP10 expression
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