Endometrial organoids to model Chlamydia infection

子宫内膜类器官模拟衣原体感染

• 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
• 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

! 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.

! 项目摘要 沙眼衣原体是导致人类性传播感染的主要细菌来源世界- 宽感染通常没有症状，如果不治疗，对女性生殖系统有长期影响。 魅力健康虽然可以用抗生素治疗，但由于缺乏长期的保护措施， 免疫力和疫苗都没有。多年来，从人类流行病学收集的数据- 逻辑研究，感染和感染的癌源性上皮细胞，如HeLa细胞的鼠模型， 有助于更好地了解感染过程。然而，存在实质性的限制， 由于样品（人和小鼠）的可及性或易处理性， 生理相关性（HeLa细胞）。在过去的十年中，3D类器官，来自成人或多能 干细胞，已经从各种组织中产生，包括女性生殖道，并显示出 紧密地概括了原始器官上皮的细胞组成和生物学/功能。在那-- 因此，类器官提供了一个独特的模型系统，以相对简单但可靠的方式研究宿主-病原体相互作用。 vant离体环境。在这里，我们建议开发一个子宫内膜类器官（EMO）- C。沙眼模型 感染我们的初步数据表明，C。沙眼可以感染并经历一个生产性的发展过程， EMO中会话周期。我们现在想进一步描述C。EMO中的沙眼感染。我们的假设是 EMO感染期间将重述衣原体发育周期的关键特征。此外，我们希望 开发操纵EMO的方法，以解决特定宿主因子在感染中的作用。总之，皮奥- 研究衣原体感染的三维EMO将有助于研究这种介质的感染过程， 重要的细菌病原体，在相关的离体模型系统中。该模型将提供一个更好的理解- 衣原体感染的分子基础，这可能有助于设计有效的基质， 旨在对抗和预防这种疾病。