Trem2+间质巨噬细胞在肺孢子菌肺炎中的免疫作用

HIV阴性的免疫抑制患者肺孢子菌肺炎（PCP）发病率逐渐升高，间质巨噬细胞（IM）在感染免疫中起重要作用，但在PCP中的具体作用机制尚不清楚。我们前期研究发现：PCP小鼠肺组织中Trem2+IM①数量在PCP中显著升高；②Egr2表达升高，ERK1/2通路激活；③显著促进Th17细胞分化。据此我们推测：PCP中Trem2+IM细胞分化增殖引起其数量增多，进而促进Th17细胞分化、分泌相关细胞因子，参与机体抗PCP的免疫作用。本课题拟在PCP小鼠模型中，应用多种分子和细胞生物学技术，阐明PC感染后肺部Trem2+IM的表型及功能特征，揭示Trem2+IM数量增多的分子机制及其促进Th17细胞分化的机制，从动物、细胞和分子水平阐述Trem2+IM在PCP中的免疫作用，为发现新的PCP治疗靶点提供理论依据。

The incidence of pneumocystis pneumonia (PCP) is increasing in HIV-negative immunosuppressed patients. Interstitial macrophage (IM) plays an important role in inflammatory immune response, but its specific mechanism in PCP remains unlear. The results of previous experiments demonstrated that: ①Trem2+ IM increased significantly in the PCP mice. ②After PC infection, the expression of Egr2 increased and ERK1/2 pathway was activated in Trem2+ IM. ③Trem2+ IM could promote the differentiation of Th17 cell. Therefore, we hypothesized that the increase in the number of Trem2+ IM was due to proliferation and differentiation, which promoted Th17 cell differentiation and secreting cytokines, hence, Trem2+ IM played a key role in anti-PCP immune response. By utilizing mice model and applying molecular and cellular biological techniques, this project aims to elucidate the immunophenotype features of Trem2+IM in PCP, explore the reasons for its increased number, and reveal the mechanisms by which Trem2+IM promote Th17 cell differentiation, which would reveal the immune mechanisms of Trem2+IM in PCP, and contribute to searching for novel therapeutic targets.