The interaction between vaginal microbiota, immunogenetics and C. trachomatis susceptibility

项目总结 阴道微生物区系被认为在防止性传播感染(STI)方面发挥着重要作用。 通过生态竞争，乳杆菌产生乳酸和靶标细菌素。 一种称为细菌性阴道病(BV)的疾病，其特征是乳杆菌枯竭。和一个 大量的厌氧菌被证明与获得性传播感染有关，包括单纯疱疹病毒- 2和HIV-1。沙眼衣原体(Chlamydia trachomatis，CT)是一种专性细胞内致病菌，与 子宫颈炎、盆腔炎，以及随后的输卵管因素不孕和异位妊娠。它是 全世界最常见的细菌性传播感染，包括在美国。流行病学数据表明， 尽管努力预防这种疾病，但最近这种疾病的发病率仍在增加，这促使人们寻找 候选疫苗和对当前CT筛查建议的更新。这样做的长期目标是 研究的目的是利用生物学和流行病学数据，通过整合 这些数据类型。我们的假设是，阴道微生物区系的组成，以及其潜在的 中断，可能导致对CT感染的易感性增加，与免疫遗传学的效果无关 可能会对这段关系产生影响。如果可以突出这样的作用，就是改变治疗和预防 CT和STI的一般指南是有根据的。但是，对当前 关于CT筛查、预防和治疗的建议需要得到关于 CT感染的自然病史。因此，本项目的目标是研究阴道的作用 微生物群在CT获取和临床表现中的独特和已经建立的年轻队列 在法国，女性前瞻性地紧随其后。一个多学科的国际研究网络已经 集中于两个特定的目标来回答这些问题：1)描述阴道的特征 两年来的微生物区系组成、丰度和动态，以及一套免疫遗传的频率 18-24岁女性队列中的生物标志物；2)对阴道微生物区系之间的相互作用进行建模， 免疫遗传因素与沙眼衣原体感染的前瞻性研究 紧随其后。在第一个目标中，我们将表征样品的阴道微生物区系(组成和丰度)。 从300名女性中，前瞻性地跟踪了四个时间点。然后，我们将在第二个目标下评估 阴道微生物区系组成和免疫遗传生物标志物对CT易感性的独立影响 感染以及症状的存在，以建立宿主-病原体-微生物区系相互作用模型。这 研究的新颖之处在于，阴道微生物群组成在CT感染易感性中的作用 从未在大规模的前瞻性队列中进行过研究。它的创新潜力在于小说的使用 分子方法，使我们能够通过整合个体来改进我们对待“健康”和“疾病”的方法 性传播感染的易感性，从而引领了个性化医疗的道路。

PROJECT SUMMARY The vaginal microbiota is thought to play a major role in preventing Sexually Transmitted Infections (STIs) through ecological competition, lactic acid and target-specific bacteriocins production by Lactobacillus species. A condition known as bacterial vaginosis (BV) characterized by the depletion of Lactobacillus spp. and an overabundance of anaerobic bacteria has been shown to be associated with acquisition of STIs including HSV- 2 and HIV-1. Chlamydia trachomatis (Ct) is an obligate intracellular bacterial pathogen associated with cervicitis, pelvic inflammatory disease, and subsequent tubal factor infertility and ectopic pregnancy. It is the most common bacterial STI worldwide, including in the United States. Epidemiological data suggest that the incidence of this disease has increased recently despite efforts to prevent it, which motivates the search for vaccine candidates and updates to current recommendations for Ct screening. The long-term goal of this research is to leverage biological and epidemiological data to adapt strategies for Ct control by integrating these data types. Our hypothesis is that the composition of the vaginal microbiota, and potentially its disruption, could lead to an increased susceptibility to Ct infection, independent of the effect immunogenetics may have on this relationship. If such a role could be highlighted, a change to the treatment and prevention guidelines for Ct and STI in general would be warranted. However, modification to the current recommendations for Ct screening, prevention and treatment would need to be supported by information on the natural history of Ct infection. Therefore, the objective of this project is to study the role of the vaginal microbiota in Ct acquisition and clinical presentation in a unique and already established cohort of young women prospectively followed in France. A multidisciplinary international research network has been assembled to answer these questions by focusing on two specific aims: 1) Characterize the vaginal microbiota composition, abundance and dynamics over 2 years, and the frequency of a set of immunogenetic biomarkers in a cohort of 18-24 years old women; 2) Model the interactions between the vaginal microbiota, immunogenetic factors and C. trachomatis infection using a cohort of 18-24 years old women prospectively followed. In the first aim, we will characterize the vaginal microbiota (composition and abundance) of samples from 300 women prospectively followed at four time points. We will then evaluate under the second aim the independent effects of vaginal microbiota composition and immunogenetic biomarkers on susceptibility to Ct infection as well as presence of symptoms, in order to build host-pathogen-microbiota interaction models. This research is novel in that the role of the vaginal microbiota composition in the susceptibility to Ct infection has never been studied in a large-scale prospective cohort. Its innovative potential lies in the use of novel molecular methods that allow us to refine our approach to “health” and “disease” by integrating individual predisposition to STIs, thus leading the way for personalized medicine.