Endometrial organoids to model Chlamydia infection

子宫内膜类器官模拟衣原体感染

基本信息

批准号：
9807600
负责人：
ISABELLE DERRE
金额：
$ 8.08万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-16 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9807600
关键词：
3-Dimensional Address Adult Affect Antibiotic Therapy Antibiotics Architecture Bacteria Bacterial Infections Biological Assay Biological Models Biology Cells Cervix Uteri Chlamydia Chlamydia Infections Chlamydia trachomatis Coculture Techniques Cytosol Data Development Disease Elements Endometrial Environment Epithelial Cells Epithelium Female Goals Hela Cells Hormones Human Immune Immunity In Vitro Infection Integration Host Factors Lead Left Malignant Neoplasms Medical Membrane Methods Modeling Molecular Monitor Mus Organ Organelles Organoids Physiological Pluripotent Stem Cells Process Proteins Protocols documentation Reproductive Health Role Sampling Sexual Transmission Sexually Transmitted Diseases Stimulus System T-Lymphocyte Testing Therapeutic Tissues Vaccines combat design epidemiology study interest mouse model neutrophil pathogen pathogenic bacteria prevent reconstitution reproductive organ reproductive tract tissue/cell culture

项目摘要

! 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.

！项目概要沙眼衣原体是世界上细菌源性人类性传播感染的主要原因宽的。感染通常是无症状的，如果不及时治疗，会对女性生殖产生长期影响。归纳健康。虽然可以用抗生素治疗，但由于缺乏长期保护，再感染率很高对感染的免疫力，并且没有疫苗。多年来，从人类流行病学中收集的数据逻辑研究、感染的小鼠模型和受感染的癌症衍生上皮细胞，例如 HeLa 细胞，有助于更好地了解感染过程。然而，存在很大的限制使用当前可用的模型，由于样本（人和小鼠）的可访问性或易处理性或生理相关性（HeLa 细胞）。在过去的十年中，源自成人或多能干细胞的 3D 类器官干细胞是从包括女性生殖道在内的各种组织中产生的，并被证明可以密切概括原始器官上皮的细胞组成和生物学/功能。那里- 因此，类器官提供了一个独特的模型系统，以相对简单但相关的方式研究宿主与病原体的相互作用。凡特离体环境。在这里，我们建议开发子宫内膜类器官（EMO）——沙眼衣原体模型的感染。我们的初步数据表明，沙眼衣原体可以感染并进行生产性发育。 EMO 中的总周期。我们现在想要进一步确定 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主要特征将在 EMO 感染期间重现。另外，我们想要开发操纵 EMO 的方法来解决特定宿主因素在感染中的作用。总而言之，pio- 对 3D EMO 的衣原体感染进行研究将有助于研究这种介质的感染过程。在相关的离体模型系统中，这是极其重要的细菌病原体。该模型将提供更好的理解衣原体感染的分子基础知识，这可能有助于设计有效的策略共同努力对抗和预防这种疾病。