Interaction of Chalmydia with Innate Immune Receptors

衣原体与先天免疫受体的相互作用

• 批准号: 7031654
• 负责人: Robin R Ingalls
• 金额: $ 31.44万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7031654
• 关键词: Chlamydia trachomatis; bactericidal immunity; cell line; chlamydial disease; clinical research; epithelium; human subject; immunologic receptors; inflammation; pelvic inflammatory disease; phagocytes; receptor binding; reproductive system infection; toll like receptor

DESCRIPTION (provided by the applicant): Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection in the United States. Infection with CT usually remains localized to the lower genital tract where it can produce urethral or cervical discharge. However, if left untreated, the infection can ascend to the upper genital tract producing salpingitis, perihepatitis and pelvic inflammatory disease (PID) in women. The resultant tissue damage from the inflammatory response is believed to result in fallopian tube scarring, tubal infertility and ectopic pregnancy. In spite of its clinical importance, little is known about the early immune responses to chlamydia. An investigation into the molecular basis of cellular activation by CT, including a characterization of the innate immune receptors and secondary mediators that initiate and coordinate the subsequent inflammatory response, has never been undertaken. We hypothesize that the interactions between specific chlamydial ligands and their innate immune receptors leads to the development of localized inflammation in the genital tract, and therefore the subsequent tissue damage associated with PID. The goals of this application are to identify the specific cellular receptors and adaptor proteins that are responsible for creating an inflammatory environment during chlamydial infection, and to determine the mechanism by which the host inflammatory response is initiated during infection of both epithelial cells and monocytes/macrophages. We will focus on defining the role of the Toll-like receptors (TLRs) and their adaptor proteins in chlamydial pathogenesis, and have proposed the following specific aims: (1) To characterize the interactions between TLRs and CT during a productive infection of epithelial cells and phagocytic cells; (2) To identify the signaling pathways activated in epithelial cells and phagocytic cells during CT infection; (3) To determine the cellular changes that follow primary infection with CT. These studies should yield novel insights into the pathogenesis of chlamydial infections, as well as the innate immune defenses of the lower female genital tract. A better understanding of the immune response in this compartment could pave the way for the development of better therapeutic agents and mucosal vaccines to combat the immediate and long-term consequences of chlamydial infections.

描述（由申请人提供）：沙眼衣原体（CT）是美国最常见的细菌性传播感染。CT感染通常局限于下生殖道，在那里它可以产生尿道或宫颈分泌物。然而，如果不及时治疗，感染可上升到上生殖道，在妇女中产生输卵管炎、周围肝炎和盆腔炎（PID）。炎症反应导致的组织损伤被认为会导致输卵管瘢痕、输卵管不孕和异位妊娠。尽管它具有临床重要性，但对衣原体的早期免疫反应知之甚少。CT对细胞活化的分子基础的研究，包括先天免疫受体和启动和协调随后炎症反应的次级介质的表征，从未进行过。