Mucosal and peripheral immune responses to chlamydial heat shock proteins in women infected with Chlamydia trachomatis

Abstract

SummaryMost of the studies on 60-kDa and 10-kDa chlamydial heat shock proteins (HSPs) to date have been carried out with blood lymphocytes or serum antibody responses, which do not provide a clear picture of the actual pathogenesis as they do not differentiate primary infection from recurrent infection. Thus, in the present study induction of the immune response was evaluated by studying lymphoproliferation of both cervical and peripheral lymphocytes to synthetic peptides of cHSP60, cHSP10 and major outer membrane protein (MOMP) antigen. In addition, cervical antibody prevalence to MOMP antigen, cHSP60 and cHSP10 and cytokine levels in cervical washes was also determined. Positive proliferative responses of cervical lymphocytes to cHSP10 peptide were significantly higher (P < 0·05) in women with recurrent infections and that to MOMP antigen were significantly higher in primary infection. On proliferation of PBMCs with the above antigens, no significant difference was observed between primary and recurrent infection. Prevalence of cervical IgG and IgA antibodies to Chlamydia trachomatis was significantly higher (P < 0·05) during primary infection than recurrent infections. In contrast, prevalence of IgG and IgA antibodies to cHSP10 and IgG antibodies to cHSP60 was higher during recurrent infections than primary infections. Interferon (IFN)-g levels were significantly higher in cervical washes of women with recurrent infection and correlated strongly with cHSP60 antibody titres. Our data thus suggest that mucosal responses are more appropriate in understanding the pathogenesis of chlamydial infection and IFN-g could be involved in the modulation of immune responses towards chlamydial infection directly, by causing acute inflammation, or indirectly through modulation of HSP expression.

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

“…IL-17 and IL-22 were five and three times as high in the cervical secretions of C. trachomatis-positive women (n ϭ 27) as in negative controls (n ϭ 17) (50). Titers of IgG and IgA antibodies to C. trachomatis EBs were higher in the cervical washes of C. trachomatis-positive fertile women during primary infection than during recurrent infection (49). However, the cervical titer of IgG to specific chlamydial antigens (cHSP60 and cHSP10) was higher in a recurrent infection than in a primary infection, which is what would be expected (49).…”

“…Titers of IgG and IgA antibodies to C. trachomatis EBs were higher in the cervical washes of C. trachomatis-positive fertile women during primary infection than during recurrent infection (49). However, the cervical titer of IgG to specific chlamydial antigens (cHSP60 and cHSP10) was higher in a recurrent infection than in a primary infection, which is what would be expected (49). Flow cytometric analysis of lymphocytes present at the cervixes of C. trachomatis-infected women identified the increased presence of a unique cell type, ␣4␤7 ϩ CLA ϩ memory T cells (51).…”

“…Analysis of immune factors by a multiplex immunoassay in cervical-vaginal lavage fluids of women with acute C. trachomatis infection (n ϭ 5) attending an STD clinic compared to those of controls with no infections (n ϭ 13) revealed significantly higher levels of IL-1␤, lactoferrin, TNF-␣, IL-8, vascular endothelial growth factor, granulocyte-colony stimulating factor (CSF), IL-10, IL-3, IL-7, IL-12, and IL-6 (48). In another study in India, IFN-␥ levels were significantly higher only in women with recurrent C. trachomatis infections than in controls but not higher than in those with primary infections (49). IL-17 and IL-22 were five and three times as high in the cervical secretions of C. trachomatis-positive women (n ϭ 27) as in negative controls (n ϭ 17) (50).…”

Correlation Between Chlamydia trachomatis IgG and Pelvic Adherence Syndrome

“…Cohen et al, (2005) found that select peripherical blood mononuclear cell lymphoproliferative responses to Chlamydia EBS and heat shock protein 60 (cHSP60) correlated with protection against incident Chlamydia but not with a reduction in incident chlamydial infection. Cervical lymphoproliferative response to cHSP10 were higher in reccurent infection, while lymphoproliferative response to OmpA was higher in primary infection (Agrawal et al, 2007). The presence of OmpA A type E protein favour the persistence of infection at 1 year follow up (Morre et al, 2002), as well as infection load (a quantitative measure of persistence organism burden and pressumably a surogate for Chlamydia trachomatis replication.…”

Development of a vaccine for Chlamydia trachomatis: challenges and current progress

“…119 It has also been reported that the levels of IFN-γ were significantly higher in the cervical washes of women with recurrent chlamydial infection, as compared to the cytokine levels from women with primary chlamydial genital infections. 120 In a recent study of 250 women, 59 of whom had TFI, C. trachomatis-infected cells produced significantly higher levels of the IL-12B subunit, p40 than uninfected cells, providing evidence that genetic variation in the IL-12 cytokine family affects C. trachomatis-specific immune responses. 121 Finally, as noted by Mabey et al, "an important difference between ocular and genital infection is that in the eye the damaging sequelae occur at the site of infection, the conjunctival epithelium" while "by contrast in the female genital tract, the major sequelae develop in the fallopian tubes and not at the cervix, which is the site of inoculation".…”