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：
10596516
负责人：
ISABELLE DERRE
金额：
$ 23.11万
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/10596516
关键词：
3-Dimensional Address Adverse effects Affect Antibiotics Bacteria Bacterial Infections Binding Biological Biological Models Biology Biomedical Engineering Biomimetics Cell Culture Techniques Cells Characteristics Chlamydia Chlamydia Infections Chlamydia trachomatis Collaborations Cytosol Ectopic Pregnancy Endocrine Environment Epithelial Cells Epithelium Equilibrium Estradiol Goals Gonadal Steroid Hormones Growth Homeostasis Human 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 Productivity 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 infection rate long-term sequelae microbiome 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.

项目摘要沙眼衣原体是全球细菌起源性传播感染的主要原因。不疫苗可用，感染通常是无症状的，如果未治疗，长期后遗症具有对妇女生殖健康的不利影响。感染的主要部位是宫颈上皮，其中这些细菌在膜结合的室内的宿主细胞胞质溶胶中复制，称为包含。防止建立衣原体复制生态位的干预措施将减少阴道脱落（即传播）并提升到上部生殖道（即长期病理）。它越来越理解，感染时组织的状态最有可能决定感染的结果。但是，对组织内的单个细胞集体启动的固有和外在因素知之甚少。人类流行病学研究，感染的鼠和细胞培养模型已被用于获得更好的了解这些过程；但是，这些模型存在很大的局限性。解决这个问题 GAP，与仿生模型核心密切合作，我们将使用人类的三维仿生基质衣原体感染的宫颈阴道模型并研究性激素对沙眼曲霉的影响感染。我们将评估细菌生长（AIM 1），组织完整性和生理学（AIM 2）和免疫响应（目标3）。总体暴露于体内重构的宫颈阴道组织在其生理上感染性衣原体的环境将提供一个独特的模型系统，以表征性激素是否以及如何表征影响对沙眼梭菌感染的敏感性。从长远来看，该模型将适用于研究与任何性传播病原体有关的基本过程，将提供相对简单且成本的测试新疗法以控制性传播感染传播的有效方法。