宿主不同靶器官中新生隐球菌侵袭力差异的影响机制

项目名称： 宿主不同靶器官中新生隐球菌侵袭力差异的影响机制

项目编号： No.31270181

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 朱红梅

作者单位： 中国人民解放军第二军医大学

项目金额： 85万元

中文摘要： 新生隐球菌是重要的机会致病真菌，临床以中枢神经系统症状为主，常引起致死性脑膜炎或脑膜脑炎。课题组前期研究发现，新生隐球菌对动物模型脑、肺、肝等不同靶器官组织具有不同侵袭力，而这种侵袭性差异甚至在某些重要毒力相关基因被敲除、相关毒力因子表达被削弱后仍然存在，说明宿主防御机制在不同靶器官受新生隐球菌侵袭状态的差异中至少起到了与毒力因子同样重要的作用。本研究拟在前期研究基础上，从宿主各靶器官防御屏障相关的细胞凋亡、细胞骨架改变、细胞代谢等方面，经由构建的体内外模型，采用蛋白组学、基因工程等技术手段，通过研究各靶组织与新生隐球菌相互作用前后S100A10、Peroxiredoxin I等关键蛋白及相关细胞因子的表达变化，结合病原菌毒力相关的表观遗传改变，对宿主防御机制行进一步研究，以揭示宿主不同靶器官中新生隐球菌侵袭力差异的影响机制，从新的角度探讨新生隐球菌"嗜中枢性"感染的可能机制。

中文关键词： 新生隐球菌；发病机理；侵袭力；宿主；防御

英文摘要： Cryptococcus neoformans is an important opportunistic pathogenic fungus which have partiality for central nervous invasion, and usually cause fatal meningitis or meningoencephalitis. Majority pathogenetic studies of cryptococcosis laid stress on virulence-associated factors of C. neoformans at present. Besides confirming the importance of such C.n virulence factors in cryptococcal infection, our previous study also revealed C.n' various invasive presentations in host's different organs. The invasive variety still existed even while some virulence-associated genes of C. n being knocked out. This phenomenon suggested that host defense might at least play an equally important role in pathogenesis of cryptococcosis. Based on our previous work, combining with the study of cryptococcal virulence, we focus more on some key proteins(e.g. S100A10、Peroxiredoxin I, et al.)and cytokines in host organic defense-related cellular apoptosis, cytoskeleton changes and cellular metabolism in this item. Adopting techniques of proteomics and gene engineering, via in vitro model and in vivo cryptococcal infection model, We would study the influence mechanism of Cryptococcus neoformans' various invasive presentations in host's different organs. Furthermore, our work would be also helpful in providing a new possiable explanation besid

英文关键词： Cryptococcus neoformans；pathogenesis；invasion；host；defense