M1巨噬细胞外泌体来源的lncRNA-LOC107985785介导的STAT1正反馈信号通路在隐球菌病中的作用及机制研究

隐球菌病的临床结局主要基于宿主的免疫状态，M1型巨噬细胞是机体免疫系统抵抗病原体的重要环节，研究发现外泌体在宿主抗感染免疫中具有多重调节功能。前期研究表明，隐球菌感染后M1巨噬细胞外泌体可诱导原始巨噬细胞呈M1表型；芯片显示该外泌体中LOC107985785明显增高，上调巨噬细胞内LOC107985785可增加STAT1表达。本项目拟进一步研究（1）细胞实验上，感染隐球菌后M1巨噬细胞来源外泌体中的LOC107985785对巨噬细胞表型的影响；（2）信号通路上，感染隐球菌后M1巨噬细胞来源外泌体中的LOC107985785对巨噬细胞表型的具体调控机制；（3）分子层面上，感染隐球菌后M1巨噬细胞对外泌体中LOC107985785表达的调控机制；（4）小鼠模型中，感染隐球菌后M1巨噬细胞外泌体中的LOC107985785对小鼠隐球菌感染进程的影响。本项目将为隐球菌致病机制与免疫治疗提供新方向。

The clinical outcomes of cryptococcosis mainly depend on the host's immune status. M1-polarized macrophages are the key regulators during the host's protective immunity. Studies have found that exosomes have multiple regulatory functions in host anti-infective immunity. .Our previous studies shown that M1 macrophage-derived exosome after cryptococcal infection induced the original macrophage to be M1 phenotype. Microarray showed that LOC107985785 in the exosome was significantly increased, and upregulation of LOC107985785 in macrophages could increase the expression of STAT1. This project intends to further study (1) the effect of LOC 107985785 on macrophage phenotype in M1 macrophage-derived exosome after cryptococcus infection (2) the specific regulatory mechanism of LOC 107985785 in M1 macrophage-derived exosome after cryptococcus infection (3) the regulatory mechanism of M1 macrophage on LOC 107985785 expression after cryptococcus infection (4) The effect of LOC 107985785 in the exosome on the progress of cryptococcal infection in mice. This project will provide a new direction for cryptococcosis immunotherapy.