嗜肺军团菌(Legionella pneumophila, L.pneumophila)是临床上致病性最强的细菌之一，可以引起咳嗽、发烧以及严重的呼吸衰竭等症状，对公共健康造成了极大威胁。L.pneumophila对抗生素极高的耐药率使得寻找新的治疗方案成为目前的研究热点。本项目组在前期工作中发现在人巨噬细胞THP-1中过表达PTPN14能促进细胞发生凋亡，并伴随有线粒体形态变化及拷贝数增加等现象；而PTPN14敲降后细胞无明显凋亡，细胞呈现细菌易感的表型。因此，本项目拟在细胞和成体两个模型基础之上，采用活细胞成像、液相色谱-串联质谱以及透射电镜等多种技术手段，从凋亡的引发和调控等多个角度，探究PTPN14通过影响线粒体稳态从而介导巨噬细胞凋亡在清除L.pneumophila的作用机制，研究结果将为临床上L.pneumophila的预防和治疗提供潜在的药物靶点。

Legionella pneumophila (L.pneumophila) is one of the most pathogenic bacteria in clinic. It can cause cough, fever, severe respiratory failure and other symptoms, posing a great threat to public health. The high resistance rate of L.pneumophila to antibiotics makes it a hot topic to find a new treatment. In our previous work, it was found that overexpression of PTPN14 in THP-1 human macrophages could promote apoptosis, accompanied by changes in mitochondrial morphology and an increase in copy number. However, after knockdown of PTPN14, there was no obvious apoptosis, and the cells showed a bacterial susceptible phenotype. Therefore, by using a variety of technical means, such as living cell imaging, LC-MS/MS, and transmission electron microscopy, the project intends to construct cell and animal models, and to explore the mechanism of PTPN14 in clearing L.pneumophila by influencing mitochondrial homeostasis from various perspectives, such as the initiation and regulation of apoptosis. The results will provide potential drug targets for the prevention and treatment of L.pneumophila in clinic.