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.

中文翻译：

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GPR183对感染的下调限制了巨噬细胞中结核分枝杆菌的早期感染和细胞内复制。

GPR183 / EBI2是在淋巴器官中定位B细胞以及T细胞和其他免疫细胞迁移的关键趋化受体。在这里，我们证明了在Mtb感染过程中诱导的巨噬细胞中GPR183的下调抑制了细菌的早期感染和细胞内复制。GPR183的过度表达或天然配体的刺激会促进巨噬细胞中Mtb的复制，而其拮抗剂的治疗会抑制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，Tyr-256的取代消除了GPR183对Mtb早期感染和巨噬细胞复制的促进作用。总之，我们证明了除了趋化性受体的已知作用外，