Cellular Microbiology of Chlamydia pneumoniae

肺炎衣原体的细胞微生物学

• 批准号: 6663824
• 负责人: Richard S Stephens
• 金额: $ 34.09万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 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 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6663824
• 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。广泛的，长期的研究目标是确定C。肺炎的发病机制，促进冠状动脉疾病。本申请的研究重点是C.肺炎与哺乳动物宿主细胞在急性和持续感染期间的相互作用。假设C.肺炎杆菌产生引起宿主细胞应答的组分，并且是随后的宿主细胞应答，包括促炎趋化因子、生长因子和凝血因子，其介导发病机制和动脉疾病。持续性感染的重要作用，衣原体感染的特点，对细胞反应和分期慢性炎症和随之而来的组织损伤的焦点环境将进行评估。这些研究的意义在于鉴定致病的细胞介质和引起这些反应的衣原体产物，从而通过鉴定用于诊断检测和疫苗或化学干预的新靶点为控制和诊断提供新的方法。具体目标将利用寡核苷酸和DNA阵列格式进行研究，以平行测量约30，000个人类基因和1，100个C的转录变化。pneumoniae基因将在已知被患病动脉组织中的衣原体感染的细胞（包括血管内皮细胞、平滑肌细胞和巨噬细胞）中检测人细胞反应。具体目的是：1）确定C.肺炎。2)对C.肺炎引起的宿主细胞基因转录的变化。3)表征C.在持续感染期间和在不同细胞类型中生长期间，4)鉴别衣原体产物并检测持续表达的衣原体。pneumoniae基因产物诱导宿主细胞应答的能力。