Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, China; NHC Key Laboratory of Human Disease Comparative Medicine, China; Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, China; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, China; Tuberculosis Center, Chinese Academy of Medical Sciences (CAMS), Beijing, China.
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, China; NHC Key Laboratory of Human Disease Comparative Medicine, China; Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, China; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, China; Tuberculosis Center, Chinese Academy of Medical Sciences (CAMS), Beijing, China.
Microb Pathog. 2020 Aug;145:104234. doi: 10.1016/j.micpath.2020.104234. Epub 2020 Apr 28.
GPR183/EBI2 is a key chemotactic receptor for the positioning of B cells in lymphoid organs, and also for the migration of T cells and other immune cells. Here, we demonstrate that the downregulation of GPR183 in macrophage induced during Mtb infection restrains the bacterial early infection and intracellular replication. Overexpression of GPR183 or stimulation with its natural ligand favors Mtb replication in macrophage, while treatment with its antagonist represses both Mtb early infection and intracellular replication. With mutational analysis, we find that substitution of Asp-73, Arg-83, Tyr-112, Tyr-256 abolished the promotive effect of GPR183 on Mtb early infection and replication in macrophage. In conclusion, we demonstrated that beside the known role of chemotaxis receptor, GPR183 also functions directly in the interaction between macrophage and Mtb in a cell-autonomous way.
GPR183/EBI2 是定位 B 细胞在淋巴器官中的关键趋化性受体，也是 T 细胞和其他免疫细胞迁移的关键趋化性受体。在这里，我们证明了 Mtb 感染期间巨噬细胞中 GPR183 的下调抑制了细菌的早期感染和细胞内复制。GPR183 的过表达或其天然配体的刺激有利于巨噬细胞中的 Mtb 复制，而用其拮抗剂处理则抑制 Mtb 的早期感染和细胞内复制。通过突变分析，我们发现 Asp-73、Arg-83、Tyr-112 和 Tyr-256 的取代消除了 GPR183 对巨噬细胞中 Mtb 早期感染和复制的促进作用。总之，我们证明了除了已知的趋化性受体作用外，GPR183 还以细胞自主的方式直接在巨噬细胞与 Mtb 的相互作用中发挥作用。
