Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai School of Medicine, New York, NY, USA.
J Reprod Immunol. 2013 Sep;99(1-2):80-7. doi: 10.1016/j.jri.2013.07.003. Epub 2013 Aug 8.
Chlamydia trachomatis infection is one of the most prevalent bacterial STIs in the USA and worldwide, and women with C. trachomatis infection are at increased risk of acquiring HIV. Because immune activation at the genital mucosa facilitates HIV/SIV infection, C. trachomatis-mediated cytokine induction may contribute to increased HIV transmission in asymptomatic women. To begin to elucidate the mechanisms, we longitudinally analyzed profiles of innate immune factors and HIV infectivity in genital secretions from anatomically specific sites in asymptomatic women during C. trachomatis infection and post-antibiotic treatment. We found higher levels of cytokines and chemokines in endocervical secretions than vaginal secretions. Compared with the convalescent state, G-CSF, IL-1α, and RANTES were elevated in endocervical secretions, IFN-γ and TNF-α were elevated in vaginal secretions, and IFNγ, IL-1β, and MIP1-α were elevated in cervicolavage fluid (CVL), before adjustment of multiple comparisons. Elevated endocervical levels of IP-10 and MCP-1 were associated with the use of hormonal contraception in infected women after successful treatment, suggesting the role of hormonal contraception in inflammation independent of STIs. Importantly, soluble factors found in endocervical secretions during infection enhanced HIV infectivity while no difference in HIV infectivity was found with vaginal secretions or CVL during infection or at convalescence. Taken together, the profiles of immune mediators and in vitro HIV infectivity indicate that the endocervical and vaginal mucosa are immunologically distinct. Our results underscore the importance of considering anatomical site and local sampling methodology when measuring mucosal responses, particularly in the presence of C. trachomatis infection.
沙眼衣原体感染是美国和全球最常见的细菌性性传播感染之一，感染沙眼衣原体的女性感染艾滋病毒的风险增加。由于生殖器黏膜的免疫激活促进了艾滋病毒/猴免疫缺陷病毒的感染，沙眼衣原体介导的细胞因子诱导可能导致无症状女性的艾滋病毒传播增加。为了开始阐明这些机制，我们在沙眼衣原体感染和抗生素治疗后，对无症状女性解剖学特定部位的生殖器分泌物中的固有免疫因子和艾滋病毒感染性进行了纵向分析。我们发现，宫颈分泌物中的细胞因子和趋化因子水平高于阴道分泌物。与恢复期相比，G-CSF、IL-1α 和 RANTES 在宫颈分泌物中升高，IFN-γ 和 TNF-α 在阴道分泌物中升高，IFNγ、IL-1β 和 MIP1-α 在宫颈管冲洗液（CVL）中升高，在进行多次比较调整之前。感染后成功治疗的感染妇女中，宫颈内 IP-10 和 MCP-1 的水平升高与使用激素避孕有关，这表明激素避孕在独立于性传播感染的炎症中发挥作用。重要的是，感染期间宫颈分泌物中发现的可溶性因子增强了艾滋病毒的感染性，而在感染期间或恢复期，阴道分泌物或 CVL 中未发现艾滋病毒感染性的差异。总之，免疫介质和体外艾滋病毒感染性的特征表明，宫颈和阴道黏膜在免疫学上是不同的。我们的研究结果强调了在测量黏膜反应时考虑解剖部位和局部采样方法的重要性，尤其是在存在沙眼衣原体感染的情况下。
