迷走神经影响肺部微环境调控流感病毒感染、炎症和免疫反应

项目名称： 迷走神经影响肺部微环境调控流感病毒感染、炎症和免疫反应

项目编号： No.91542105

项目类型： 重大研究计划

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 苏枭

作者单位： 中国科学院上海巴斯德研究所

项目金额： 70万元

中文摘要： 流感病毒诱发急性肺损伤发病的分子机制尚不清楚，死亡率仍居高不下。神经对感染、炎症和免疫的调控是近年来生命科学领域的研究热点。既往我们研究发现迷走神经可释放乙酰胆碱调控肺部微环境并通过α7 nAChR影响酸吸入和细菌感染诱发的急性肺损伤。据此，我们假设迷走神经活性可以影响流感病毒感染时肺部微环境进而影响肺部的区域免疫。我们要探讨是否迷走神经可以通过α7 nAChR影响肺上皮细胞、免疫细胞对流感病毒的识别和清除？是否影响上述细胞IFN-β的诱导以及ISRE活性？是否影响巨噬细胞M2型极化？是否影响肺部免疫代谢？是否影响肺部淋巴细胞和天然淋巴样细胞的募集或诱导等科学问题？因此，我们将应用分子生物学、免疫学、神经生理学等先进手段来深入研究迷走神经如何调控肺部微环境，并通过α7 nAChR影响流感病毒肺部感染、炎症和免疫的分子机制。研究成果将为流感病毒诱发的急性肺损伤治疗提供新靶点。

中文关键词： 迷走神经；α7烟碱型乙酰胆碱受体；流感病毒；肺微环境；急性肺损伤

英文摘要： The pathogenesis of influenza A virus (IAV)-induced acute lung injury (ALI) is still unclear and its mortality remains high. How nervous system regulates infection, inflammation and immunity is a recent hotspot of research in the life science. Previously, we have found that vagus nerve could regulate pulmonary microenvironment via acetylcholine which activates α7 nicotinic acetylcholine receptor (α7 nAChR), therefore modulates acid aspiration or Gram negative bacteria-induced ALI. Here, we hypothesize that activity of vagus nerve would regulate lung microenvironment during IAV infection and consequently affect IAV replication and pulmonary inflammation and immunity. As such, we aim to study several key scientific questions: whether vagus nerve via α7 nAChR would regulate recognition and clearance of IAV in the lung epithelial and immune cells, affect induction of IFN-β and activity of ISRE, play a role in the M2 polarization of macrophages, have an impact on lung immune metabolism, and influence the recruitment or induction of lymphocytes or innate lymphoid cells during IAV-induced ALI, etc. To approach this, we will utilize molecular biological, immunological, neurophysiological and other advanced approaches. The ultimate goal is to understand how vagus nerve through α7 nAChR regulates pulmonary microenvironment and determines the outcome of IAV-induced ALI. The findings will provide us novel therapeutic targets for treating IAV-induced ALI.

英文关键词： Vagus nerve;α7 nicotinic acetylcholine receptor;Influenza A virus;Pulmonary microenvironment;Acute lung injury