The Effects of Sex Hormones on Chlamydia Infection

项目总结 沙眼衣原体是全世界细菌性传播感染的主要原因。不是 疫苗是可用的，感染通常是无症状的，如果不治疗，长期的后遗症会有 对妇女生殖健康的不利影响。感染的主要部位是宫颈上皮，在那里 这种细菌在宿主细胞胞浆中复制，在一个称为包裹体的膜结合的隔间内。 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)和上升到上生殖道(即长期病理)。它越来越多 认识到感染时组织的状态最有可能决定感染的结果； 然而，人们对共同启动组织内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，已经被用来获得更好的 对这些过程的理解；然而，这些模型有很大的局限性。要解决这个问题 GAP，在与仿生模型核心的密切合作下，我们将使用一种人体三维仿生 沙眼衣原体感染的宫颈阴道模型及性激素对沙眼衣原体的影响 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)和免疫 回应(目标3)。综上所述，体外重组宫颈阴道组织暴露于其生理状态 感染衣原体的环境将提供一个独特的模型系统来表征性激素是否以及如何 影响沙眼衣原体感染的易感性。从长远来看，这一模型将适用于 与任何性传播病原体相关的基本过程，将提供相对简单和成本- 测试控制性传播感染传播的新疗法的有效方法。

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.