肺炎衣原体感染小鼠模型的CD4+ T细胞凋亡的研究

项目名称： 肺炎衣原体感染小鼠模型的CD4+ T细胞凋亡的研究

项目编号： No.31272575

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 农业科学

项目作者： 王成明

作者单位： 扬州大学

项目金额： 80万元

中文摘要： 肺炎衣原体感染主要引起人的非典型性肺炎，而且和冠心病等慢性炎症性疾病相关。CD4+ T细胞的调控是肺炎衣原体致病机理的关键，但具体机制不详。我们在预试验中发现，肺炎衣原体感染的C57BL/6小鼠比A/J有着显著低下的T细胞反应和更严重的肺脏疾病,以及更高的CD4+T细胞凋亡率。我们推测"抑制AICD介导的CD4+ T细胞凋亡会增加Th细胞数量，同时促进Th1反应向Th2转换"。我们首先观察细胞凋亡抑制剂能否降低C57BL/6小鼠的高CD4+T细胞凋亡率。然后用统计学方法综合分析如下因子和CD4+ T细胞凋亡的相关性：小鼠基因组成,衣原体感染与对照，肺脏疾病，肺脏衣原体清除率，33个目标基因（9个细胞凋亡基因，10个T/Th1/Th2细胞和14个炎症调控因子）的mRNA水平，流式细胞和TUNEL试验结果和不同细胞凋亡抑制剂的使用。此研究将为衣原体感染的Th1/Th2极化和疫苗研制提供新思路。

中文关键词： 肺炎衣原体；CD4+ T细胞；细胞凋亡；FRET-PCR；流行病学

英文摘要： Chlamydia (C.), an omnipresent obligate intracellular bacterial pathogen, infects a wide range of host species. Infections with C. pneumoniae，causing respiratory infections such as bronchitis and pneumonia, have also been consistently associated with chronic inflammatory diseases such as atherosclerosis, Alzheimer's disease and asthma. These associations promote the analysis of mechanisms that regulate disease in response to C. pneumoniae infections. Our previous research showed that reduced early T cell responses associate with enhanced disease in C57BL/6 mice as compared to A/J mice. A possible reason for the delayed T cell responses is increased activation-induced cell death (AICD) of CD4+ T cells as suggested by modeling of T helper cell regulation. We stipulate that suppression of T cell apoptosis increases the Th cell population size, and shifts the response towards Th2 because of greater resistance of Th2 cells than Th1 cells against AICD-mediated apoptosis. In this study, we aim to test the concept of apoptosis-mediated regulation of T helper cells, and its consequences on C. pneumoniae-induced lung disease. We will first evaluate if the naturally protected A/J mice have a lower apoptotic rate of CD4+ T cells in infected lungs than in susceptible C57BL/6 mice. Subsequently, we attempt to reduce th

英文关键词： Chlamydia pneumoniae；CD4 T cell；apoptosis；FRET-PCR；epidemiology