Chlamydia pneumoniae persistance in the blood vessel

 描述（由申请方提供）：肺炎衣原体是一种人类呼吸道病原体，可引起人类急性和慢性呼吸道感染。累积的证据也表明C.肺炎是心血管疾病的危险因素，并有助于动脉粥样硬化（一种慢性炎症疾病）的发病机制。慢性/持续性衣原体感染的特征是炎症、纤维化和瘢痕形成，并且慢性/持续性感染难以治疗。 其定义为生物体以不可培养但存活的状态存在，并且可以由各种因素如细胞因子、营养剥夺和各种抗生素诱导。持久性是由于衣原体发育周期的停滞，其中代谢活跃的非感染性形式（网状体）不会重组为感染性原体。一个重要的问题是，是否持续发生在人类衣原体感染，并刺激免疫病理反应。根据在无法培养微生物的标本中检测到衣原体抗原/DNA以及抗生素治疗失败，存在人类持续性衣原体感染的证据。然而，没有明确的诊断标志物的持续感染检测活的微生物。C.肺炎抗原/DNA经常在动脉粥样硬化病变中的泡沫细胞内检测到，泡沫细胞是充满脂质的血管细胞。重要的是，在高脂血症小鼠模型中，C.肺炎感染加速动脉粥样硬化病变的进展;抗菌治疗没有效果，并且仍然存在微生物的证据。本提案的总体目标是确定高脂血症是否促进活性C的持续存在。肺炎微生物在血管中，这是难治的抗生素治疗。这些研究可以确定持续性感染的诊断标志物，并提供对心血管疾病二级预防临床试验中抗生素治疗缺乏有益效果的见解。

 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.