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

Abstract

Most 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)-gamma 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-gamma could be involved in the modulation of immune responses towards chlamydial infection directly, by causing acute inflammation, or indirectly through modulation of HSP expression.

Fig. 1

Proliferative responses (stimulation index) of cervical lymphocytes and peripheral blood mononuclear cells (PBMCs) to (a) chlamydial heat shock proteins (cHSP)10 and (b) cHSP60 in women with primary or recurrent Chlamydia trachomatis infection and controls. The horizontal line in the middle of the box is the median value of the responses and the lower (upper) 25th (75th) percentile.

Fig. 2

Immunoglobulin A (IgA) antibodies to synthetic peptides corresponding to epitopes of (a) chlamydial heat shock proteins (cHSP)10 and (b) cHSP60 in cervical washes of women with primary or recurrent infection and controls. The horizontal line indicates the lower boundary of a positive antibody response.