Agrawal T, Vats V, Salhan S, Mittal A
Institute of Pathology, ICMR, Safdarjang Hospital Campus, New Delhi, India.
Clin Exp Immunol. 2007 Jun;148(3):461-8. doi: 10.1111/j.1365-2249.2007.03357.x.
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.
迄今为止,大多数关于60 kDa和10 kDa衣原体热休克蛋白(HSPs)的研究都是针对血液淋巴细胞或血清抗体反应进行的,由于这些研究无法区分初次感染和复发感染,因此不能清晰地呈现实际发病机制。因此,在本研究中,通过研究宫颈和外周淋巴细胞对沙眼衣原体热休克蛋白60(cHSP60)、沙眼衣原体热休克蛋白10(cHSP10)和主要外膜蛋白(MOMP)抗原合成肽的淋巴细胞增殖情况来评估免疫反应的诱导。此外,还测定了宫颈洗液中针对MOMP抗原、cHSP60和cHSP10的宫颈抗体流行率以及细胞因子水平。复发感染女性的宫颈淋巴细胞对cHSP10肽的阳性增殖反应显著更高(P < 0.05),而初次感染时对MOMP抗原的阳性增殖反应显著更高。用上述抗原刺激外周血单核细胞(PBMCs)增殖时,初次感染和复发感染之间未观察到显著差异。沙眼衣原体宫颈IgG和IgA抗体的流行率在初次感染时显著高于复发感染(P < 0.05)。相比之下,复发感染时针对cHSP10的IgG和IgA抗体以及针对cHSP60的IgG抗体的流行率高于初次感染。复发感染女性的宫颈洗液中干扰素(IFN)-γ水平显著更高,且与cHSP60抗体滴度密切相关。因此,我们的数据表明,黏膜反应更适合用于理解衣原体感染的发病机制,并且IFN-γ可能通过引发急性炎症直接参与对衣原体感染免疫反应的调节,或通过调节HSP表达间接参与。