Cellular Microbiology of Chlamydia pneumoniae

肺炎衣原体的细胞微生物学

• 批准号: 6943446
• 负责人: Richard S Stephens
• 金额: $ 34.2万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6943446
• 关键词: Chlamydiaceae; atherosclerosis; auxotrophy; bacterial proteins; blood banks; cellular pathology; chlamydial disease; clinical research; gene expression; genetic transcription; heat shock proteins; host organism interaction; human tissue; interferon gamma; laboratory mouse; lipopolysaccharides; microarray technology; microorganism growth; pathologic process; polymerase chain reaction; tissue /cell culture; tryptophan

DESCRIPTION (provided by applicant): Atherosclerosis has been associated with infection by the bacterial pathogen Chlamydia pneumoniae. The broad, long-term goal of the proposed studies is to define the mechanisms of C. pneumoniae pathogenesis that promote coronary artery disease. The research focus of this application is the molecular characterization of C. pneumoniae interactions with mammalian host cells during acute and persistent infection. The hypothesis is that C. pneumoniae produce components that elicit responses by the host cell and it is the consequent host cell responses including proinflammatory chemokines, growth factors and coagulation factors that mediate pathogenesis and arterial disease. The important role of persistent infection, characteristic of chlamydial infections, on cellular responses and staging the focal environment for chronic inflammation and consequent tissue damage will be evaluated. The significance of these studies is the identification of the cellular mediators of pathogenesis and the chlamydial products that elicit these responses thereby informing new approaches for control and diagnosis by identifying novel targets for diagnostic detection and vaccine or chemical intervention. The specific aims will be investigated utilizing oligonucleotide and DNA array formats to measure changes in transcription in parallel for approximately 30,000 human genes and 1,100 C. pneumoniae genes. Human cellular responses will be tested in cells known to be infected by chlamydia in diseased arterial tissues including vascular endothelial cells, smooth muscle cells and macrophages. The specific aims are: 1) Determine the spectrum of cellular responses to infection by C. pneumoniae. 2) Validate the protein expression of C. pneumoniae-induced changes in host cell gene transcription. 3) Characterize gene expression profiles for C. pneumoniae during persistent infection and during growth in different cell types. 4) Identify chlamydial products and test persistently-expressed C. pneumoniae gene products for their ability to induce host cell responses.

描述（由申请人提供）： 动脉粥样硬化与细菌病原体肺炎衣原体感染有关。拟议研究的广泛、长期目标是确定肺炎衣原体促进冠状动脉疾病的发病机制。该应用的研究重点是急性和持续感染期间肺炎衣原体与哺乳动物宿主细胞相互作用的分子特征。假设肺炎衣原体产生引起宿主细胞反应的成分，并且随后的宿主细胞反应包括介导发病机制和动脉疾病的促炎趋化因子、生长因子和凝血因子。将评估持续感染（衣原体感染的特征）对细胞反应以及对慢性炎症和随后的组织损伤的局灶环境进行分期的重要作用。这些研究的意义在于鉴定了发病机制的细胞介质和引起这些反应的衣原体产物，从而通过确定诊断检测和疫苗或化学干预的新靶标，为控制和诊断的新方法提供信息。具体目标将利用寡核苷酸和 DNA 阵列形式并行测量约 30,000 个人类基因和 1,100 个肺炎衣原体基因的转录变化。人类细胞反应将在患病动脉组织中已知被衣原体感染的细胞中进行测试，包括血管内皮细胞、平滑肌细胞和巨噬细胞。具体目标是： 1) 确定细胞对肺炎衣原体感染的反应谱。 2) 验证肺炎衣原体诱导的宿主细胞基因转录变化的蛋白表达。 3) 表征肺炎衣原体在持续感染和不同细胞类型生长过程中的基因表达谱。 4) 鉴定衣原体产物并测试持续表达的肺炎衣原体基因产物诱导宿主细胞反应的能力。