Chlamydia pneumoniae persistance in the blood vessel

 描述(申请人提供)：肺炎衣原体是一种人类呼吸道病原体，可导致人类急性和慢性呼吸道感染。累积的证据还表明，肺炎衣原体是心血管疾病的危险因素，并在动脉粥样硬化的发病机制中起作用，动脉粥样硬化是一种慢性炎症疾病。慢性/持续性衣原体感染的特征是炎症、纤维化和疤痕形成，慢性/持续性感染难以治疗。体外持续的衣原体感染有 定义为生物体处于不可培养但可存活的状态，可由各种因素诱导，如细胞因子、营养剥夺和各种抗生素。持续性是衣原体发育周期停止的结果，在该周期中，代谢活跃的非传染性形式(网状小体)不会重组为具有感染性的基本体。一个重要的问题是，在人类衣原体感染中是否存在持续性，并刺激免疫病理反应。人类持续感染衣原体的证据是基于在无法培养该生物体的标本中检测到衣原体抗原/DNA，以及抗生素治疗失败。然而，目前还没有明确的持续感染诊断标志来检测活的生物体。肺炎衣原体抗原/DNA经常在动脉粥样硬化病变中的泡沫细胞内检测到，泡沫细胞是一种富含脂质的血管细胞。重要的是，在高脂血症的小鼠模型中，肺炎衣原体的感染加速了动脉粥样硬化病变的进展；抗菌治疗没有效果，生物体的证据仍然存在。这项建议的总体目标是确定高脂血症是否促进了对抗生素治疗无效的肺炎链球菌在血管中的存活。这些研究可能确定持续性感染的诊断标记物，并对在心血管疾病二级预防的临床试验中缺乏抗生素治疗的有益影响提供洞察。

 DESCRIPTION (provided by applicant): Chlamydia pneumoniae is a human respiratory pathogen that causes acute and chronic respiratory tract infections in humans. Cumulative evidence also has suggested that C. pneumoniae is a risk factor for cardiovascular disease and contributes to the pathogenesis of atherosclerosis, a disease of chronic inflammation. Hallmarks of chronic/persistent chlamydial infection are inflammation, fibrosis and scarring and chronic/persistent infections are difficult to treat. Persistent chlamydial infections in vitro are defined as the presence of the organism in a non-cultivable, but viable state, and can be induced by various factors such as cytokines, nutritional deprivation and various antibiotics. Persistence results from the arrest of the chlamydial developmental cycle in which the metabolically active, non-infectious form (the reticulate body) does not reorganize into the infectious elementary body. An important question is whether persistence occurs in human chlamydial infection and stimulates immunopathologic responses. Evidence of persistent Chlamydia infection in humans exists based on detection of chlamydial antigen/DNA in specimens from which the organism cannot be cultured and by antibiotic treatment failure. However, there are no clear diagnostic markers of persistent infection detecting viable organisms. C. pneumoniae antigen/DNA is detected frequently in atherosclerotic lesions, within foam cells, which are lipid laden vascular cells. Importantly, in mouse models of hyperlipidemia, C. pneumoniae infection accelerates atherosclerotic lesion progression; antimicrobial treatment has no effect, and evidence of the organism remains. The overall goal of this proposal is to determine if hyperlipidemia promotes persistence of viable C. pneumoniae organisms in the blood vessel, which are refractory to antibiotic treatment. These studies may identify diagnostic markers of persistent infection and provide insight into the lack of beneficial effects of antibiotc treatment in clinical trials on secondary prevention of cardiovascular disease.