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.

呢项目摘要沙眼衣原体是人类性传播的细菌来源感染的主要原因 - 宽的。感染通常是无症状的，如果未经治疗，感染对女性的重复产生长期后果导管健康。尽管可以用抗生素治疗，但由于缺乏长期保护性，再感染率很高免疫感染和疫苗不可用。多年来，从人类流行病中收集的数据逻辑研究，感染的鼠模型和感染的癌症衍生的上皮细胞，例如HeLa细胞，有助于更好地理解感染过程。但是，有很大的限制由于可访问性或可及性，因此可用的模型（人和小鼠）或生理相关性（HELA细胞）。在过去的十年中干细胞已是由各种组织产生的，包括女性生殖道，并证明密切概括了原始器官上皮的细胞组成以及生物学/功能。那里- 首先，器官提供了一个独特的模型系统，可以在相对简单但相关的相对 Vant Ex Vivo环境。在这里，我们建议开发子宫内膜器官（EMO） - C.沙眼模型感染。我们的初步数据表明，沙眼梭状芽胞盘可以感染和经历生产力的发展。 emo中的tal循环。现在，我们想进一步表征emo中沙眼曲霉感染的特征。我们的假设是在情绪感染期间，将概括衣原体发育周期的关键特征。此外，我们想要开发操纵emo以解决特定宿主因素在感染中的作用的方法。完全，pio- 3D EMO的Neering衣原体感染将有助于研究这种医疗的感染过程在相关的离体模型系统中，重要的细菌病原体。该模型将为您提供更好的应用衣原体感染的分子基本原理的结合，这可能有助于设计有效的策略战斗以战斗和预防这种疾病。