Endometrial organoids to model Chlamydia infection

好了！ 项目总结 沙眼衣原体是人类细菌性传播感染的主要原因。 很宽。感染通常是无症状的，如果不治疗，会对女性生殖系统产生长期后果。 引导性健康。虽然可以用抗生素治疗，但由于缺乏长期保护措施，再感染率很高。 对感染具有免疫力，也没有疫苗可用。多年来，从人类流行病收集的数据- 逻辑研究，小鼠感染模型和受感染的癌细胞来源的上皮细胞，如HeLa细胞， 有助于更好地了解感染过程。然而，它有很大的局限性。 在目前的模型下，由于样本(人和小鼠)的可及性或可操作性，或 生理相关性(HeLa细胞)。在过去的十年里，3D有机化合物，来源于成体或多能性 干细胞是从包括女性生殖道在内的各种组织中产生的，并显示出 严密概括原始器官上皮的细胞组成和生物学/功能。在那里- 因此，有机化合物提供了一种独特的模型系统来研究寄主-病原体的相互作用，这是一种相对简单而又真实的方法。 Vant体外环境。在这里，我们建议建立子宫内膜器质性(EMO)-沙眼衣原体模型。 感染的可能性。我们的初步数据表明，沙眼衣原体可以感染并经历一种生产性的发育-- EMO中的Tal循环。我们现在想要进一步描述EMO中沙眼衣原体感染的特征。我们的假设是 衣原体发育周期的关键特征将在EMO感染期间概述。此外，我们希望 开发操纵EMO的方法，以解决特定宿主因素在感染中的作用。总而言之，皮奥- 通过对3DEMO衣原体感染的研究，将有助于进一步了解本研究的感染过程。 重要的细菌病原体，在相关的体外模型系统中。该模型将提供更好的适应性 阐明衣原体感染的分子基础，有助于设计有效的防治策略。 为抗击和预防这种疾病而努力。

! PROJECT SUMMARY Chlamydia trachomatis is the leading cause of human sexually transmitted infections of bacterial origin world- wide. Infections are often asymptomatic and, if left untreated, have long-term consequences on female repro- ductive health. Although treatable with antibiotics, reinfection rates are high due the lack of long-term protective immunity from infection, and vaccines are not available. Over the years, data collected from human epidemio- logical studies, murine models of infection and infected cancer-derived epithelial cells, such as HeLa cells, have contributed to a better understanding of the infection process. However, there are substantial limitations with the current models available, due to accessibility to or tractability of the samples (human and mice) or physiological relevance (HeLa cells). Over the past decade, 3D organoids, derived from adult or pluripotent stem cells, have been generated from various tissues, including the female reproductive tract, and shown to closely recapitulate the cellular composition, and biology/functionality of the original organs' epithelium. There- fore, organoids offer a unique model system to study host-pathogen interaction in a relatively simple, yet rele- vant ex vivo environment. Here, we propose to develop an endometrial organoid (EMO) - C. trachomatis model of infection. Our preliminary data indicate that C. trachomatis can infect and undergo a productive developmen- tal cycle in EMO. We now want to further characterize C. trachomatis infection in EMO. Our hypothesis is that key features of Chlamydia developmental cycle will be recapitulated during EMO infection. In addition, we want to develop methods to manipulate EMO to address the role of specific host factors in infection. Altogether, pio- neering Chlamydia infection of 3D EMO will be instrumental in investigating the infection process of this medi- cally important bacterial pathogen, in a relevant ex vivo model system. This model will provide a better appre- ciation of the molecular fundamentals of Chlamydia infection, which could help in the design of efficient strate- gies to combat and prevent the disease.