IMMUNITY AND LATENCY TO CHLAMYDIAL INFECTIONS

衣原体感染的免疫力和潜伏期

基本信息

批准号：
6693849
负责人：
Gerald Irwin Byrne
金额：
$ 28.03万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-10-01 至 2006-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6693849
关键词：
Chlamydia trachomatis bactericidal immunity chlamydial disease cytokine genetic strain genetically modified animals heat shock proteins histopathology immunocytochemistry laboratory mouse latent bacterial disease microorganism culture microorganism growth pelvic inflammatory disease tissue /cell culture virulence

项目摘要

Members of the genus Chlamydia, a group of obligate intracellular procaryotic pathogens, are important causes of human infectious diseases. Chlamydia pneumoniae recently has been implicated in the initiation and development of atherosclerosis. Chlamydia trachomatis is a major cause of preventable infectious blindness and the leading cause of bacterial sexually transmitted diseases (STD). Upper genital tract complications in females represents a significant women's health issue. Silent pelvic inflammatory disease (PID) can lead to tubal obstructive infertility. This serious disease will require extensive investigation to understand the pathogenic processes that cause irreparable damage of the reproductive tract in women during their child-bearing years. It is important to discern pathologic changes that accompany atherosclerosis, trachoma, PID and tubal obstructive disease as these events actually occur in infected people, but studies involving human populations do not lend themselves well to carefully controlled experimental conditions. Therefore we propose to continue our work using a variety of cell culture systems (human and murine) to study general features of persistent intracellular chlamydial growth which may be common to all chronic chlamydial infections and pursue the murine-C. trachomatis genital tract in vivo model to study the hypothesis that persistent chlamydiae may contribute to the development of upper genital tract disease. This hypothesis will be tested by building on our experience related to the effects of immune response regulated cytokines on chlamydial host cell activation that results in enhanced expression of chlamydial stress response proteins together with new information on the effects of stress response proteins on the disease process. We also will study how these fundamental events in the basic biology of chlamydiae relate to chronic disease as exemplified by upper genital tract infections in mice. The work plan will comprise 4 specific aims, 2 of which are intended to broaden our cell culture knowledge of persistent (stressed) chlamydial growth and 2 of which will apply this knowledge to an in vivo system. Results will lead to increased information concerning how the basic biology of chlamydiae directly impacts the disease process and the development of chronic chlamydial disease.

衣原体属的成员是一组专性细胞内原核病原体，是人类传染病的重要原因。最近，肺炎衣原体与动脉粥样硬化的发生和发展有关。沙眼衣原体是可预防的感染性失明的主要原因，也是细菌性性传播疾病 (STD) 的主要原因。女性上生殖道并发症是一个重要的女性健康问题。无症状盆腔炎（PID）可导致输卵管阻塞性不孕。这种严重的疾病需要进行广泛的调查，以了解对育龄妇女生殖道造成不可挽回损害的致病过程。辨别伴随动脉粥样硬化、沙眼、盆腔炎和输卵管阻塞性疾病的病理变化非常重要，因为这些事件实际上发生在感染者身上，但涉及人群的研究并不适合仔细控制的实验条件。因此，我们建议继续使用各种细胞培养系统（人类和小鼠）来研究持续性细胞内衣原体生长的一般特征，这可能是所有慢性衣原体感染所共有的，并追踪小鼠-C。沙眼衣原体生殖道体内模型研究了持续存在的衣原体可能导致上生殖道疾病发展的假设。这一假设将通过建立我们与免疫反应调节细胞因子对衣原体宿主细胞激活的影响相关的经验（导致衣原体应激反应蛋白表达增强）以及应激反应蛋白对疾病过程影响的新信息进行检验。我们还将研究衣原体基础生物学中的这些基本事件如何与慢性疾病相关，例如小鼠上生殖道感染。该工作计划将包括 4 个具体目标，其中 2 个旨在扩大我们对衣原体持续（应激）生长的细胞培养知识，其中 2 个旨在将这些知识应用于体内系统。研究结果将带来更多有关衣原体基础生物学如何直接影响疾病过程和慢性衣原体疾病发展的信息。