隐球菌病是条件致病真菌导致的感染，治疗棘手，病死率高，致病机理主要与宿主免疫缺陷有关，其中巨噬细胞活化缺陷是关键因素之一。前期研究发现，隐球菌病患者外周血circRNA存在异常表达谱；巨噬细胞中高表达的circ_0091746与M2极化标志Arg1正相关；生物信息分析发现miR-6848-5p有多个circ_0091746和Arg1的结合位点；过表达miR-6848-5p可抑制Arg1表达，从而影响巨噬细胞极化状态。本项目拟进一步研究(1)circ_0091746对巨噬细胞抗新生隐球菌免疫反应中功能的影响；(2)circ_0091746对巨噬细胞抗新生隐球菌免疫反应中M1/M2极化的调控机制；(3)巨噬细胞抗新生隐球菌免疫反应中circ_0091746表达的调控机制；(4)利用隐球菌小鼠模型，研究circ_0091746对隐球菌病进程的影响。本研究将为隐球菌病的免疫疗法提供新的依据。

Cryptococcosis is a kind of conditional fungi infection with high mortality due to therapy limitations. The pathogenesis is mainly related to the host's immune deficiency and the key factor is macrophage activation defect. The preliminary study found there was an abnormal expression profile of circRNAs in the peripheral blood of cryptococcal patients; circ_0091746 in macrophages was significantly higher and positively correlated with Arg1 which is the M2 polarized marker; Bioinformatics analysis revealed that there were multiple miR-6848-5p sequences for circ_0091746 and Arg1; overexpression of miR-6848-5p inhibited the expression of Arg1, which affected macrophage polarization. This project aims to study (1) the effects of circ_0091746 on macrophage function during Cryptococcus neoformans infection; (2) regulatory mechanism of circ_0091746 in M1/M2 polarization during Cryptococcus neoformans infection; (3) the regulation mechanism of macrophages circ_0091746 expression during Cryptococcus neoformans infection; (4) role of circ_0091746 on cryptococcosis process via cryptococcal mouse model. This study will provide a new theoretical basis for the immunotherapy of cryptococcosis.