Chlamydia pneumoniae persistance in the blood vessel

肺炎衣原体在血管中持续存在

• 批准号: 9031212
• 负责人: LEE ANN CAMPBELL
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9031212
• 关键词: Acute; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antigens; Arterial Fatty Streak; Atherosclerosis; Azithromycin; Blood Vessels; Cardiovascular Diseases; Cells; Characteristics; Chlamydia Infections; Chlamydophila pneumoniae; Chronic; Chronic Disease; Cicatrix; Clinical Trials; Coronary heart disease; DNA; Detection; Development; Endothelial Cells; Exposure to; Fatty acid glycerol esters; Fibrosis; Foam Cells; Genetic Transcription; Goals; Growth; Human; Hyperlipidemia; In Vitro; Infection; Inflammation; Interferon Type II; Intervention; Iron; Lipids; Measurement; Modeling; Mus; Nucleic Acids; Organism; Outcome; Pathogenesis; Patients; Pattern; Phenotype; Prevention trial; Process; Production; Refractory; Respiratory Tract Infections; Risk Factors; Secondary Prevention; Smooth Muscle Myocytes; Specimen; Staging; Testing; Tissues; Treatment Failure; advanced disease; antimicrobial; base; cytokine; design; diagnostic biomarker; factor C; insight; macrophage; mouse model; nutrient deprivation; pathogen; prevent; public health relevance; rRNA Precursor; respiratory; response

 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.

 描述（由申请人提供）：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，累积证据还表明肺炎衣原体是心血管疾病的危险因素，并导致动脉粥样硬化的发病机制。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，并且慢性/持续性感染难以治疗。体外衣原体感染是 定义为生物体处于不可培养但可存活的状态，并且可由多种因素诱导，例如细胞因子、营养缺乏和各种抗生素。衣原体发育周期的停滞导致其持续存在，其中代谢活跃，非传染性形式（网状体）不会重组为传染性基本体。一个重要的问题是，人类衣原体感染是否会持续存在并刺激持续的免疫病理反应。人类衣原体感染的存在是基于无法培养该生物体的标本中的衣原体抗原/DNA 以及抗生素治疗失败，但是，没有检测到活的肺炎衣原体抗原/DNA 的持续感染的明确诊断标记。经常在动脉粥样硬化病变的泡沫细胞（富含脂质的血管细胞）中检测到，重要的是，在高脂血症的小鼠模型中，肺炎衣原体感染会加速动脉粥样硬化病变的进展；该提案的总体目标是确定高脂血症是否会促进血管内存活的肺炎衣原体微生物的持续存在，而这些微生物对抗生素治疗是无效的。深入了解临床试验中抗生素治疗对心血管疾病二级预防缺乏有益作用。