耐甲氧西林金黄色葡萄球菌（MRSA）肺炎因其耐药性使得发病率和致死率高居不下。因此，寻找新的干预靶点是突破MRSA肺炎治疗瓶颈的关键。申请人前期发现肥大细胞参与机体对甲氧西林敏感金葡菌的抗菌免疫（Cell Prolif，2019，IF: 5.039；J Infect Dis，2018，IF: 5.045）。基于此，本项目拟进一步探索肥大细胞在MRSA肺炎中的免疫调控机制。预实验提示：MRSA肺炎中肥大细胞缺陷小鼠抗菌功能显著减弱，而细胞miRNA-369-3p抑制SOCS5和p-mTOR的同时，也参与吞噬和脱颗粒进程。为此，我们提出科学假说：miRNA-369-3p调控肥大细胞自噬参与对MRSA的抗菌免疫。本课题将利用不同种类基因敲除小鼠构建MRSA肺炎模型，探讨miRNA-369-3p调控肥大细胞自噬的分子机制，明确细胞自噬在MRSA肺炎中的作用，进而为疾病防治提供新的治疗靶点和策略。

The presence of drug resistance to methicillin-resistant Staphylococcus aureus (MRSA) pneumonia keeps the morbidity and mortality rates high. Therefore, finding new intervention targets is pivotal to improve MRSA pneumonia treatment. The applicant has previously found that mast cells participate in antibacterial immunity to methicillin sensitive Staphylococcus aureus (Cell Prolif, 2019, IF: 5.039; J Infect Dis, 2018, IF: 5.045). Based on this, this project intends to further explore the immune modulatory mechanism of mast cells in MRSA pneumonia. The pre-experiment showed that mast cell-deficient mice showed worsened antibacterial effects when suffering from MRSA pneumonia. In vitro data suggested that miR-369-3p was involved in the processes of phagocytosis and degranulation while inhibiting the expression of SOCS5 and p-mTOR. For all this, we propose scientific hypothesis: mast cell autophagy regulated by miRNA-369-3p participates in the antibacterial immunity to MRSA. In the current project, murine model of MRSA pneumonia will be established using different kinds of gene-knockout mice. Besides, in vitro cell tests will study the molecular mechanism of mast cell-derived miRNA-369-3p in regulation of autophagy. The role of mast cell autophagy in MRSA pneumonia will be explored. Therefore, it would be a prospective study which provides new therapeutic targets and strategies for disease control.