Chlamydia pneumoniae Antigens of Biological Significance

具有生物学意义的肺炎衣原体抗原

• 批准号: 6624069
• 负责人: LEE ANN CAMPBELL
• 金额: $ 34.11万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6624069
• 关键词: Chlamydia trachomatis; antireceptor antibody; atherosclerosis; bacterial antigens; bacterial pneumonia; bacterial vaccines; carbohydrate receptor; chlamydial disease; communicable disease diagnosis; confocal scanning microscopy; enzyme linked immunosorbent assay; flow cytometry; host organism interaction; human tissue; immunoaffinity chromatography; immunopathology; immunoprecipitation; laboratory mouse; mannose 6 phosphate; monoclonal antibody; polymerase chain reaction; serology /serodiagnosis; tissue /cell culture; vaccine development; virulence; western blottings; yeast two hybrid system

DESCRIPTION (provided by the applicant): Chlamydia pneumoniae is a human respiratory pathogen that causes 5 percent to 10 percent of pneumonia, bronchitis, and sinusitis. Virtually everyone is infected in his or her lifetime and reinfection is common. Infection is difficult to treat even with sensitive antibiotics. Chronic infection is common and has been associated with asthma, reactive airway disease, Reiter's syndrome, erythema nodosum, and sarcoidosis. The potential public health impact of infection with this pathogen is underscored by the association of C. pneumoniae with atherosclerosis and related clinical manifestations such as coronary heart disease, carotid artery stenosis, aortic aneurysm, claudication, and stroke. If C. pneumoniae infection plays a role in atherogenesis, there will be an urgent need to facilitate diagnosis and develop strategies for intervention and prevention. The overall goal of this proposal is two fold. First, C. pneumoniae specific antigens that are recognized during human infection will be exploited to facilitate serodiagnosis and identify putative vaccine candidates. The second goal is to define chlamydial/host cell interactions that lead to entry and survival of C. pneumoniae in host cells relevant to atherosclerosis. The specific focus will be on the interaction of the chlamydial glycan moiety with carbohydrate binding receptors on the host cell. Importantly, infection of epithelial cells can be inhibited with N-linked high mannose type oligosaccharide, the major component of the glycan. The novel hypothesis to be tested is that C. pneumoniae enters through the mannose-6 phosphate receptor by binding to the site involved in transport of phosphomannosylated residues to the lysosome and this differs from C. trachomatis, which utilizes the mannose receptor. The ultimate goals of these studies are to identify C. pneumoniae specific antigens to facilitate laboratory diagnosis and virulence factors playing a role in pathogenesis to guide vaccine development or develop anti-adhesive strategies for prevention of infection.

描述（由申请人提供）：肺炎衣原体是一种人类 引起 5% 至 10% 肺炎的呼吸道病原体， 支气管炎和鼻窦炎。几乎每个人都在他或她的身体里被感染 终生和再感染很常见。即使使用药物也很难治疗感染 敏感抗生素。慢性感染很常见，并且与 哮喘、反应性气道疾病、赖特综合征、结节性红斑和 结节病。这种病原体感染的潜在公共卫生影响 肺炎衣原体与动脉粥样硬化的关联强调了这一点 冠心病、颈动脉等相关临床表现 狭窄、主动脉瘤、跛行和中风。如果肺炎衣原体感染 在动脉粥样硬化形成中发挥作用，因此迫切需要促进 诊断并制定干预和预防策略。整体 该提案的目标有两个。首先，肺炎衣原体特异性抗原 在人类感染期间被识别将被利用以促进 血清诊断并确定假定的候选疫苗。第二个目标是 定义导致衣原体进入和存活的衣原体/宿主细胞相互作用。 宿主细胞中的肺炎链球菌与动脉粥样硬化有关。具体重点将 研究衣原体聚糖部分与碳水化合物结合的相互作用 宿主细胞上的受体。重要的是，上皮细胞的感染可以 主要成分N-连接高甘露糖型寡糖抑制 聚糖。要测试的新假设是肺炎衣原体进入 通过甘露糖 6 磷酸受体结合参与的位点 将磷酸甘露糖基化残基转运至溶酶体，这不同于 沙眼衣原体，利用甘露糖受体。最终目标 这些研究旨在鉴定肺炎衣原体特异性抗原，以促进 实验室诊断和毒力因子在发病机制中发挥作用 指导疫苗开发或制定抗粘附策略以预防 感染。