Ly6C+Ly6G+双阳性CD4+T细胞调控肺脏中性粒细胞抗胸膜肺炎放线杆菌感染的作用及机制

由于细菌耐药性增加、疫苗缺乏广谱保护性及混合感染等问题存在，基于提高机体抗感染免疫能力的细菌性肺炎防治新策略成为目前国内外研究的热点和竞争焦点。申请人前期使用胸膜肺炎放线杆菌（APP）诱导的小鼠细菌性肺炎模型，发现了一种具有抗感染作用的新型Ly6C+Ly6G+CD4+T细胞亚群，其抗感染功能的发挥可能与其调控中性粒细胞的趋化和活化有关，然而具体调控机制尚不明确。本项目拟通过小鼠体内和体外实验，研究该新型细胞亚群的组织定位、增殖与活化特性；明确其对中性粒细胞趋化和活化的影响及调控机制，以揭示该新型细胞亚群在抗APP感染中的作用机制，并做进一步的普适性分析。不仅为提高机体抗APP感染能力新策略的研发提供新的细胞和分子靶点，还将为从机体抗感染免疫角度防治细菌性肺炎提供新思路和参考。

Due to the increasing drug resistance of bacteria, lack of broad spectrum of protective vaccines, and mixed infections, the new prevention and treatment strategy of bacterial pneumonia based on improving the anti-infection immunity in the lung is becoming the research focus worldwide. Recently, a novel lung-specific CD4+ T cell subset with Ly6C+Ly6G+ phenotype has been identified in Actinobacillus pleuropeumoniae (APP) infected mouse model by the applicant, which has a protective role against bacterial pneumonia. Its anti-infection role is likely to be achieved by regulating the recruitment/activation of neutrophils. However, the underlying regulatory mechanism is currently unknown. Therefore, through both in vivo and in vitro experiments on mice, the present project will investigate the spatial distribution and proliferation/activation properties of the new cell subset, clarify its regulation on neutrophilic recruitment/activation and the underlying regulatory mechanism, aiming to reveal the anti-infection mechanism in APP induced pneumonia, following with further universality analysis. The present project will not only provide new cellular and molecular targets for the development of novel strategies for improving the immune resistance to APP infection but also provide new ideas and references for the prevention and treatment of bacterial pneumonia from the perspective of anti-infection immunity.