Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.
Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
J Int AIDS Soc. 2019 Aug;22 Suppl 6(Suppl Suppl 6):e25346. doi: 10.1002/jia2.25346.
Globally, sexually transmitted infections (STI) affect >300 million people annually, and are a major cause of sexual and reproductive health complications in women. In this commentary, we describe how STIs interact with the immune and non-immune cells, both within and below the cervicovaginal mucosal barrier, to cause inflammation, which in turn has been associated with increased HIV acquisition risk.
STIs have a major impact on the female genital mucosa, which is an important biological and physical barrier that forms the first line of defence against invading microorganisms such as HIV. Pattern recognition of STI pathogens, by receptors expressed either on the cell surface or inside the cell, typically triggers inflammation at the mucosal barrier. The types of mucosal responses vary by STI, and can be asymptomatic or culminate in the formation of discharge, ulcers and/or warts. While the aim of this response is to clear the invading microbes, in many cases these responses are either evaded or cause pathology that impairs barrier integrity and increases HIV access to target cells in the sub-mucosa. In addition, innate responses to STIs can result in an increased number of immune cells, including those that are the primary targets of HIV, and may contribute to the association between STIs and increased susceptibility to HIV acquisition. Many of these cells are mediators of adaptive immunity, including tissue-resident cells that may also display innate-like functions. Bacterial vaginosis (BV) is another common cause of inflammation, and evidence for multiple interactions between BV, STIs and HIV suggest that susceptibility to these conditions should be considered in concert.
STIs and other microbes can induce inflammation in the genital tract, perturbing the normal robust function of the mucosal barrier against HIV. While the impact of STIs on the mucosal immune system and HIV acquisition is often under-appreciated, understanding their interactions of the infections with the immune responses play an important role in improving treatment and reducing the risk of HIV acquisition. The frequent sub-clinical inflammation associated with STIs underscores the need for better STI diagnostics to reverse the immunological consequences of infection.
在全球范围内，每年有超过 3 亿人感染性传播感染（STI），这些感染是女性性健康和生殖健康并发症的主要原因。在本篇述评中，我们描述了 STI 如何与免疫和非免疫细胞相互作用，包括宫颈阴道黏膜屏障内和屏障下的细胞，从而导致炎症，而炎症又与 HIV 感染风险增加有关。
STI 对女性生殖黏膜有重大影响，生殖黏膜是一个重要的生物学和物理屏障，形成了抵御 HIV 等入侵微生物的第一道防线。细胞表面或细胞内表达的受体对 STI 病原体的模式识别，通常会引发黏膜屏障的炎症反应。不同 STI 的黏膜反应类型不同，可能无症状，也可能导致分泌物、溃疡和/或疣的形成。虽然这种反应的目的是清除入侵的微生物，但在许多情况下，这些反应要么被规避，要么导致病理损伤，破坏屏障完整性，并增加 HIV 进入黏膜下靶细胞的机会。此外，对 STI 的先天反应会导致免疫细胞数量增加，包括 HIV 的主要靶细胞，这可能与 STI 和 HIV 易感性增加有关。这些细胞中有许多是适应性免疫的介质，包括组织驻留细胞，这些细胞也可能具有先天样功能。细菌性阴道病（BV）是另一种常见的炎症原因，BV、STI 和 HIV 之间存在多种相互作用的证据表明，这些情况的易感性应被视为协同考虑。
STI 和其他微生物可引起生殖道炎症，扰乱了黏膜屏障对 HIV 的正常强大功能。尽管 STI 对黏膜免疫系统和 HIV 感染的影响往往被低估，但了解这些感染与免疫反应的相互作用对于改善治疗和降低 HIV 感染风险至关重要。与 STI 相关的频繁亚临床炎症强调了需要更好的 STI 诊断方法来逆转感染的免疫后果。
