共生菌维持肺免疫稳态及其抵抗流感病毒急性肺损伤的机制研究

项目名称： 共生菌维持肺免疫稳态及其抵抗流感病毒急性肺损伤的机制研究

项目编号： No.31300753

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 李凤琦

作者单位： 中国科学技术大学

项目金额： 23万元

中文摘要： 过度免疫应答的"细胞因子风暴"效应是流感导致急性肺损伤的主要原因，然而目前尚没有控制这种过度免疫应答的有效手段。肺脏具有维持自身免疫稳态的能力，寻找肺脏负相免疫细胞及其关键分子可为缓解"细胞因子风暴"导致的损伤提供有效手段。我们在数年的前期研究中发现，自然环境饲养小鼠和SPF环境饲养小鼠对流感导致急性肺损伤的敏感性存在巨大差异；呼吸道共生菌，例如金黄色葡萄球菌，致敏能够保护小鼠抵抗流感病毒导致的肺损伤和死亡。本研究旨在进一步系统验证小鼠呼吸道共生菌维持肺脏免疫稳态并控制过度免疫应答的能力；寻找维持肺脏免疫稳态的调节性天然免疫细胞或亚群，并探明其来源、分化和功能调控等特性。在上述基础上，深入研究共生菌的核心成分与调节性天然免疫细胞上相应受体进行识别活化的分子机制，揭示调节性天然免疫细胞负相调节病理性炎症细胞的关键功能分子，为防治流感急性肺损伤提供新思路。

中文关键词： 呼吸道；共生菌；金黄色葡萄球菌；流感病毒；免疫调节

英文摘要： "Cytokine storm" effect-mediated excessive immune response is a major contributor to the acute lung injury during influenza virus infection. However, there was no effective way to control this harmful effect until now. Lung has the ability to maintain immune homeostasis, so exploring both regulatory immune cells and related key molecules in the lung may provide effective ways to attenuate "cytokine storm" effect-mediated injury. In previous study, we found that SPF mice were more sensitive to influenza-caused lung injury than mice lived in natural environment, and priming with commensal bacteria such as Staphylococcus aureus colonized in the respiratory tract could protect mice against influenza-caused lung injury and death. In this study, we aim to systematically verify the function of commensal bacteria in the respiratory tract on maintaining lung immune homeostasis and controlling excessive immune response, to explore the regulatory innate immune cell subsets maintaining lung immune homeostasis, and to ascertain the source, differentiation and function of this cell subset. Based on above, we will further study the molecular mechanism of the interaction between the core composition of commensal bacteria and the receptor expressed on regulator innate immune cell subsets, and further reveal the key functional mo

英文关键词： Respiratory tract；Commensal bacteria；S. aureus；Influenza virus；Immunological regulation