The Effects of Sex Hormones on Chlamydia Infection

项目摘要 沙眼衣原体是全世界细菌性传播感染的主要原因。没有 疫苗是可用的，感染往往是无症状的，如果不治疗，长期后遗症有 对妇女生殖健康的不利影响。感染的主要部位是子宫颈内上皮， 细菌在宿主细胞胞质溶胶中在称为内含物的膜结合区室中复制。 预防衣原体复制生态位建立的干预措施将减少阴道脱落（即， 传播）和Ascension到上生殖道（即长期病理）。显得越来越 应当理解，感染时组织的状态最有可能决定感染的结果; 然而，对组织内共同引发单个细胞的内在和外在因素知之甚少。 人类流行病学研究、小鼠和细胞培养感染模型已被用于获得更好的 然而，这些模型有很大的局限性。为了解决这个 gap，与仿生模型核心密切合作，我们将使用人类三维仿生 宫颈阴道衣原体感染模型，探讨性激素对衣原体感染的影响。沙眼衣原体 感染我们将评估细菌生长（目标1）、组织完整性和生理学（目标2）以及免疫 响应（目标3）。总之，离体重构的宫颈阴道组织在其生理条件下的暴露是有利的。 环境传染性衣原体将提供一个独特的模型系统，以表征性激素是否以及如何 影响对C.沙眼感染从长远来看，这一模式将适用于研究 与任何性传播病原体有关的基本过程，并将提供一个相对简单和成本- 测试新疗法的有效方法，以控制性传播感染的传播。

PROJECT SUMMARY Chlamydia trachomatis is the leading cause of sexually transmitted infections of bacterial origin worldwide. No vaccines are available, infections are often asymptomatic, and if left untreated, long-term sequelae have an adverse effect on women reproductive health. The primary site of infection is the endocervical epithelium, where the bacteria replicates in the host cell cytosol within a membrane-bound compartment called the inclusion. Interventions to prevent the establishment of the Chlamydia replicative niche would reduce vaginal shedding (i.e. transmission) and ascension to the upper reproductive tract (i.e. long-term pathology). It is more and more appreciated that the state of the tissue at the time of infection most likely dictates the outcome of infection; however, little is known about intrinsic and extrinsic factors that collectively prime individual cells within the tissue. Human epidemiological studies, murine and cell culture models of infection, have been used to gain a better understanding of these processes; however, there are substantial limitations with these models. To address this gap, in close collaboration with the Biomimetic Models Core, we will use a human three-dimensional biomimetic cervicovaginal model of chlamydial infection and investigate the effects of sex hormones on C. trachomatis infection. We will assess bacterial growth (Aim 1), tissue integrity and physiology (Aim 2) and the immune response (Aim 3). Altogether, the exposure of ex vivo reconstituted cervicovaginal tissue in its physiological environment to infectious chlamydiae will offer a unique model system to characterize if and how sex hormones influence susceptibility to C. trachomatis infection. In the long term, this model will be applicable to the study of fundamental processes related to any sexually transmitted pathogen and will offer a relatively simple and cost- effective way for testing novel therapies to control the spread of sexually transmitted infections.