巨噬细胞是调控机体天然免疫和获得性免疫的重要细胞。在不同的微环境、不同的细胞因子作用下，巨噬细胞可极化成不同的表型。正常功能的巨噬细胞在宿主控制细菌感染中发挥了很重要的作用。蛋白酪氨酸磷酸酶SHP2基因与许多重要的细胞生命活动密切相关，然而SHP2在肺部炎症和细菌清除中的作用及相关分子调控机制仍未得到深入的阐明。本项目将利用巨噬细胞SHP2基因定向敲除小鼠，建立不可分型流感嗜血杆菌（NTHi）肺炎模型，探索SHP2基因及其相关信号通路在巨噬细胞炎症反应和细菌清除中的作用。本研究有望阐明SHP2调控巨噬细胞极化，增强机体抗菌免疫的分子机制。我们的工作将揭示巨噬细胞极性转换和细胞功能调控的重要分子机制，为肺部细菌感染的免疫学治疗提供新的策略。

Macrophages are the key cells that mediate innate and adaptive immunity. Macrophages play a critical role in host defense against bacterial infections. Protein tyrosine phosphatase SHP2 is closely related to many important cellular activities, however the role of SHP2 in the regulation of pulmonary inflammation and bacterial clearance is largely unknown. Establishing NTHi lung infection model in macrophage-specific SHP2-/- mice, we will explore the role of the SHP2-mediated pathway in inflammatory response of macrophages and clearance of NTHi. Moreover, the molecular mechanisms of SHP2 in regualtion of macrophage polarization and antibacterial immunity will be revealed. Our work will offer new molecular mechanisms of macrophage polarization and function regulation, providing a new immunological strategy in the treatment of pulmonary bacterial infection.