Cellular Microbiology of Chlamydia pneumoniae

描述(由申请人提供)： 动脉粥样硬化与肺炎衣原体的感染有关。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。这一应用的研究重点是肺炎衣原体在急性和持续感染过程中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的成分可以引起宿主细胞的反应，而正是随后的宿主细胞反应，包括促炎性趋化因子、生长因子和凝血因子，介导了发病和动脉疾病。以衣原体感染为特征的持续感染对细胞反应和慢性炎症和随后的组织损伤的局部环境的分期的重要作用将被评估。这些研究的意义在于识别致病的细胞介质和引起这些反应的衣原体产物，从而通过识别新的诊断检测和疫苗或化学干预的靶点，为控制和诊断提供新的方法。将利用寡核苷酸和DNA阵列形式来研究特定的目标，以同时测量大约30,000个人类基因和1,100个肺炎衣原体基因的转录变化。人体细胞反应将在已知感染衣原体的细胞中进行测试，这些细胞位于患病的动脉组织中，包括血管内皮细胞、平滑肌细胞和巨噬细胞。其具体目的是：1)确定肺炎衣原体感染后的细胞反应谱。2)验证肺炎衣原体诱导宿主细胞基因转录变化的蛋白表达。3)研究肺炎衣原体在不同细胞类型中持续感染和生长过程中的基因表达谱。4)鉴定衣原体产物并检测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。

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.