miRNA-21调控功能抑制性中性粒细胞在金黄色葡萄球菌感染相关肺炎中的作用及机制研究

Currently, the S. aureus immune escape mechanism is possible the outcomes of neutrophil–bacteria interaction, but the exact mechanism is still unclear. Neutrophil is newly discovered to be changed from pro-inflammatory function into anti-inflammatory function in the microenvironment of certain microbial infections, and then plays a role in the inhibition of T-lymphocyte responses. Our study found that CD11b+Gr1intCD49d- neutrophils which were negatively correlatted with IL-17-producing CD4+ T lymphocytes were significantly increased, additionally the expression of miR-21 in CD11b+Gr1intCD49d- neutrophils was also significantly increased on day 4 postinfection. Therefore we speculate that miR-21 regulates immunosuppressive neutrophils in mice with S. aureus associated pneumonia. In this project we will focus on CD11b+Gr1int CD49d-neutrophils and try to illustrate the mechanism of miR-21 in regulating CD11b+Gr1int CD49d-neutrophils using methods of cell sorting, cell transfection, etc. Depicting the role of miR-21 in this process will be critical for us to provide new experimental evidence for the S. aureus immune escape mechanism, and to find a more effective immunotherapy to combat it.

目前金黄色葡萄球菌的免疫逃逸机制与中性粒细胞和细菌之间的相互作用密切相关，但确切机制仍未阐明。近期发现在某些微生物感染的微环境中，中性粒细胞自身功能可发生改变，由促炎功能转变为抑炎功能，并发挥T淋巴细胞应答的抑制作用。我们研究发现，在S.aureus感染小鼠第4天，一群功能抑制性CD11b+Gr1intCD49d-中性粒细胞明显增高，并抑制产IL-17的CD4+T淋巴细胞，且CD11b+Gr1intCD49d-细胞中miR-21表达水平显著增高。我们推测miR-21很可能调控了功能抑制性中性粒细胞参与S. aureus感染的肺炎。本项目拟具有抑制功能的CD11b+Gr1intCD49d-中性粒细胞作为研究对象，通过多种实验方法，研究miR-21调控功能抑制性CD11b+Gr1intCD49d-中性粒细胞的作用机制，将为阐明中性粒细胞相关的S. aureus免疫逃逸提供新的实验依据和治疗手段

目前S. aureus的免疫逃逸机制与细胞和细菌之间的相互作用密切相关，但确切机制仍未阐明。本项目以CD11b+Gr1+CD49d- 细胞作为研究对象，在前期建立S. aureus感染诱导的肺炎C57BL/6小鼠模型基础上，研究miR-21参与抑制CD4+T淋巴细胞功能的CD11b+Gr1+CD49d- 细胞的产生。通过细胞分选等实验，进一步阐明miR-21通过靶基因PTEN调控功能抑制性的CD11b+Gr1+CD49d- 细胞的作用机制。研究miR-21调控抑制功能的CD11b+Gr1+CD49d-细胞的作用机制，将为阐明中性粒细胞相关的S. aureus免疫逃逸提供新的实验依据，对肺炎的免疫治疗具有重要的指导意义。