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.

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Background: Chlamydia trachomatis infection of the female genital tract can lead to serious sequelae resulting in fertility related disorders. Little is known about the mechanism leading to Chlamydia induced pathology and factors responsible for it. As only some of the women develops reproductive disorders while majority of the women clears infection without any severe sequalae, mucosal immune response in women with or without fertility disorders was studied to identify factors which may lead to final clinical outcome of chlamydial infection.

The mobilization of myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) to the cervix during chlamydial infection is not fully understood, and the role of these cells in immunopathogenesis is largely unknown. As an effective vaccine to control chlamydial infection is currently unavailable, understanding the regulation of the local immune response becomes a necessity. Therefore, mDC and pDC populations were analysed in peripheral blood and cervical samples of controls and Chlamydia-positive women, with or without mucopurulent cervicitis (MPC). Cervical cytokines and C-reactive protein levels in serum were quantified by ELISA and the chlamydial infectious load by culture. Chlamydia trachomatis infection mobilized both mDCs and pDCs to the cervical mucosa. pDCs were recruited more often in women with MPC (p <0.05) and they correlated significantly with the chlamydial load, C-reactive protein levels and cervical interleukin-8 (IL-8) levels. Upregulation of surface expression of co-stimulatory molecules (CD80, CD83 and CD86) on cervical mDCs and pDCs was observed during chlamydial infection but was significant only for mDCs. Significantly higher levels of IL-1 beta, IL-6 and IL-8 were observed in Chlamydia-positive women with MPC; however, after therapy, IL-8 levels decreased significantly. Median numbers of mDCs after therapy were significantly higher in the cervix and blood of infected women as compared to the numbers of pDCs, which were found to be lower in the cervix after therapy. These results thus suggest that during chlamydial infection, both mDCs and pDCs are recruited to the cervix, but their number and possible immunological functions may differ with the pathological condition. pDCs were associated more often with MPC and inflammatory factors, suggesting that they may possibly be involved in the immunopathogenesis of infections due to Chlamydia.

Chlamydia trachomatis stimulates innate immune cells by activation of TLR2/TLR 4. Overall data indicate that recognition by TLR4 helps in initiation of immune response while recognition by TLR2 leads to secretion of inflammatory cytokines while iNOS-induced nitric oxide production helps in clearing Chlamydia. These results are first to provide initial insights into how innate immune response operates in human cervical monocytes upon chlamydial infection.