The Effects of Sex Hormones on Chlamydia Infection

性激素对衣原体感染的影响

基本信息

批准号：
10395583
负责人：
ISABELLE DERRE
金额：
$ 25.41万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-20 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10395583
关键词：
3-Dimensional Address Adverse effects Affect Antibiotics Bacteria Bacterial Infections Biological Biological Models Biology Biomedical Engineering Biomimetics Cell Culture Techniques Cells Characteristics Chlamydia Chlamydia Infections Chlamydia trachomatis Collaborations Cytosol Ectopic Pregnancy Endocrine Environment Epithelial Epithelial Cells Equilibrium Goals Gonadal Steroid Hormones Growth Homeostasis Human Human Microbiome Immune Immune response Immunity Individual Infection Infertility Innate Immune Response Intervention Invaded Knowledge Left Membrane Menstrual cycle Modeling Mucous Membrane Mucous body substance Mus Outcome Pathology Pelvic Inflammatory Disease Phase Physiological Physiology Predisposition Process Production Progesterone Reproductive Health Resistance to infection Role Sexual Transmission Sexually Transmitted Diseases Site Stromal Cells Structure Testing Tight Junctions Time Tissues Vaccines Vagina Woman antimicrobial peptide cell type cervicovaginal chemokine cost effective cytokine epidemiology study long-term sequelae neutrophil novel therapeutics pathogen prevent reconstitution reproductive tract response trafficking transmission process vaccine access vaginal microbiota

项目摘要

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.

项目概要沙眼衣原体是全世界细菌性性传播感染的主要原因。不疫苗已经可用，感染通常是无症状的，如果不及时治疗，会产生长期后遗症对女性生殖健康造成不良影响。主要感染部位是宫颈内膜上皮，其中细菌在宿主细胞胞浆内的膜结合区室（称为包涵体）中复制。防止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）。越来越多了认识到感染时组织的状态很可能决定感染的结果；然而，人们对组织内单个细胞共同启动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被用来获得更好的结果了解这些过程；然而，这些模型存在很大的局限性。为了解决这个问题差距，与仿生模型核心密切合作，我们将使用人体三维仿生衣原体感染的宫颈阴道模型并研究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）以及免疫响应（目标 3）。总而言之，离体重建的宫颈阴道组织在其生理学中的暴露传染性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产生影响沙眼衣原体感染的易感性。从长远来看，该模型将适用于研究与任何性传播病原体相关的基本过程，并将提供相对简单且成本低廉的方法测试控制性传播感染传播的新疗法的有效方法。