中文摘要
鲍曼不动杆菌成为院内重要的病原菌和其强大的耐药基因外,还与其与人类免疫细胞间的免疫反应有关。外膜蛋白是革兰氏阴性细菌上的主要蛋白,和宿主免疫关系密切。不同的细菌,其外膜蛋白与机体间的免疫反应不同,甚至同一细菌不同浓度外膜蛋白其免疫反应也不尽相同。中性粒细胞聚集肺组织及其NADPH噬菌细菌氧化酶系统在对抗鲍曼不动杆菌中扮演了极其重要的作用。机体免疫细胞上的toll样受体和外膜蛋白关系密切,同时TLR2影响中性粒细胞的凋亡,调节中性粒细胞在炎症部位的募集。然而鲍曼不动杆菌的外膜蛋白在鲍曼不动杆菌致病中的作用,以及对于宿主中性粒细胞功能的影响,Toll样受体是否在其中起到重要影响,目前尚不明确。本研究将构建外膜蛋白缺失的鲍曼不动杆菌突变株,研究其对中性粒细胞的募集,吞噬功能的影响,同时采用转基因小鼠进一步探讨toll样受体在介导外膜蛋白和肺中性粒细胞之间的免疫关系变化中的作用机制进行深入研究。
英文摘要
The high rate of antibiotic resistance makes A. baumannii a pathogen of high importance and concern. Therefore, further understanding of host defense and its mechanisms is necessary and might provide new possibilities for the treatment of nosocomial pneumonia. Neutrophil play a important role in pathgenesis of Acinetobacter baumannii pneumonia. Recent researches show that outer membrane proteins A can engage TLR2, inducting and regulating the cytokines via NF-kappa B. Meanwhile TLR2 pathway involves in the recruitment and enhances the phagocyte activity of neutrophils via cytokines. However, the role of OmpA in Acinetobacter baumannii pathogenesis, especially in neutrophils recruitment and phagocyte activity is not confirmed. We hypothesis that in Acinetobacter baumannii pneumonia, outer member protein A is crucial in pathegenesis via involving recruitment of neutrophil through the signal transduction pathways of Toll-like receptor 2. The mutant strain of OmpA(OmpA-/-) will be constructed and compared with the wild strain in the activity of recruitment and phagocytosis in neutrophil to research the function of OmpA in Acinetobacter baumannii pathegenesis. The mechanism of the function of OmpA in neutrophil will be studied deeply via TLR2 knockout mice.
