Reiter's syndrome mechanism of chlamydial pathogenesis

赖特综合征衣原体发病机制

• 批准号: 7046776
• 负责人: ALAN PAUL HUDSON
• 金额: $ 35.01万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7046776
• 关键词: Chlamydia trachomatis; Reiter' s syndrome; arthritis therapy; bacteria infection mechanism; bacterial genetics; bacterial proteins; cell line; chronic disease /disorder; clinical research; developmental genetics; disease /disorder etiology; genetic regulation; genetic transcription; host organism interaction; human genetic material tag; human subject; immunomodulators; immunopathology; infectious arthritis; longitudinal human study; molecular pathology; pathologic process; patient oriented research; relapse /recurrence; sexually transmitted diseases; synovial fluid

DESCRIPTION (provided by applicant): Genital infection with the bacterial pathogen Chlamydia trachomatis is associated with development of reactive arthritis (ReA). While it is clear that the process leading to joint disease is partly immunopathogenic in nature, the means by which C trachomatis initiates and maintains that process remain to be elucidated. Data from this group and others have shown that synovial Chlamydiae display unusual metabolic and transcriptional characteristics and are arrested at a late stage of the developmental cycle. Chlamydiae displaying these and other unusual biologic attributes in vivo are designated to be in the persistent state. Accumulating data further indicate that persistent C. trachomatis cells interact in an overt but poorly understood manner with their host cells. The key to development of effective therapies to treat Chlamydia-associated ReA lies in understanding the biology of chlamydial persistence, and the means by which host and pathogen interact during establishment of that state. In the studies proposed here, we define the genes and gene sets from C. trachomatis that are involved directly or indirectly in establishment and maintenance of the persistent state, using a well-characterized in vitro model of chlamydial persistence. We also, and coordinately, define the changes in expression for specific, targeted sets of host genes as a function of establishment of persistent chlamydial infection in the in vitro model of persistence. The gene sets to be targeted in these analyses will include those from the immune system, the signal transduction system, the energy transduction system, and others. Together, these studies will provide critical new insight not only into chlamydial proteins required for persistence, but also into previously unaddressed interactions between C. trachomatis and its primary host cells. Using information gained from these studies, we will determine the molecular genetic basis for differences between patients who progress to chronic disease and those who do not following genital chlamydial infection, and we define the molecular basis for the remittingrelapsing phenotype of patients with chronic Chlamydia-induced arthritis, and. These latter studies will give important information relating to host-pathogen interaction during various stages of disease progression. Taken together, the results of the studies proposed here will provide a comprehensive understanding of chlamydial persistence and host-pathogen interaction in ReA and therefore will form the foundation for design and implementation of rational strategies to treat the disease.

描述（由申请方提供）：生殖器感染细菌病原体沙眼衣原体与反应性关节炎（ReA）的发生有关。虽然很明显，导致关节疾病的过程在本质上部分是免疫病理性的，但沙眼衣原体启动和维持该过程的方式仍有待阐明。来自这个小组和其他人的数据表明，滑膜衣原体显示出不寻常的代谢和转录特征，并在发育周期的后期阶段被逮捕。在体内表现出这些和其他不寻常的生物学属性的衣原体被指定为处于持续状态。积累的数据进一步表明，持久C。沙眼细胞以明显但知之甚少的方式与它们的宿主细胞相互作用。开发治疗衣原体相关ReA的有效疗法的关键在于了解衣原体持续存在的生物学，以及宿主和病原体在建立该状态期间相互作用的方式。在本文的研究中，我们定义了C.沙眼衣原体直接或间接参与持久状态的建立和维持。我们也，并协调，定义特定的，有针对性的宿主基因集的表达的变化作为建立持续性衣原体感染的体外模型的持久性的功能。在这些分析中靶向的基因组将包括来自免疫系统、信号转导系统、能量转导系统等的基因组。总之，这些研究将提供关键的新的见解，不仅对衣原体蛋白所需的持久性，而且到以前未解决的相互作用之间的C。沙眼衣原体及其主要宿主细胞。利用从这些研究中获得的信息，我们将确定进展为慢性疾病的患者和未发生生殖道衣原体感染的患者之间差异的分子遗传基础，并确定慢性衣原体诱导的关节炎患者缓解-复发表型的分子基础。后者的研究将提供重要的信息，在疾病进展的各个阶段的宿主-病原体相互作用。总之，这里提出的研究结果将提供一个全面的了解衣原体的持久性和宿主-病原体相互作用的ReA，因此将形成合理的策略来治疗疾病的设计和实施的基础。