Chlamydia pneumoniae Antigens of Biological Significance

简介(申请人提供)：肺炎衣原体为人类 导致5%到10%肺炎的呼吸道病原体， 支气管炎和鼻窦炎。几乎每个人都感染了他或她的 终生和再感染是很常见的。即使是感染也很难治疗 敏感的抗生素。慢性感染很常见，并与 哮喘、反应性呼吸道疾病、莱特氏综合征、结节性红斑和 结节病。感染这种病原体对公众健康的潜在影响 肺炎衣原体与动脉粥样硬化和 相关临床表现，如冠心病、颈动脉 狭窄、主动脉瘤、跛行和中风。如果肺炎衣原体感染 在动脉粥样硬化的形成中起到一定的作用，将迫切需要促进 诊断并制定干预和预防策略。整体而言 这项提议的目标有两个方面。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来促进 血清诊断和确定推定的候选疫苗。第二个目标是 明确衣原体/宿主细胞的相互作用导致C。 宿主细胞肺炎与动脉粥样硬化的关系。具体的重点将是 衣原体多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-连接高甘露糖型低聚糖抑制作用 多聚糖的含量。需要检验的新假设是肺炎衣原体进入 通过与甘露糖-6磷酸受体结合到参与 磷脂残基向溶酶体的运输，这与 沙眼衣原体，它利用甘露糖受体。的最终目标 这些研究都是为了鉴定肺炎衣原体的特异性抗原，以方便 实验室诊断和毒力因子在致病机制中的作用 指导疫苗开发或制定防粘连策略以预防 感染。

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.