Downregulation of GPR183 on Infection Restricts the Early Infection and Intracellular Survival of Mycobacterium tuberculosis in Macrophage
Downregulation of GPR183 on Infection Restricts the Early Infection and Intracellular Survival of Mycobacterium tuberculosis in Macrophage
Abstract 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 survival. Overexpression of GPR183 or stimulation with its natural ligand favors Mtb survival in macrophage, while treatment with its antagonist represses both Mtb early infection and intracellular survival. 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 survival 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.
Tang Jun、Zhan Lingjun、Qin Chuan、Shi Ya?ˉnan
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Comparative Medicine Center, Peking Union Medical College (PUMC)||NHC Key Laboratory of Human Disease Comparative Medicine||Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious||Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases||Tuberculosis Center, Chinese Academy of Medical Sciences (CAMS)Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Comparative Medicine Center, Peking Union Medical College (PUMC)||NHC Key Laboratory of Human Disease Comparative Medicine||Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious||Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases||Tuberculosis Center, Chinese Academy of Medical Sciences (CAMS)Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Comparative Medicine Center, Peking Union Medical College (PUMC)||NHC Key Laboratory of Human Disease Comparative Medicine||Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious||Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases||Tuberculosis Center, Chinese Academy of Medical Sciences (CAMS)Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Comparative Medicine Center, Peking Union Medical College (PUMC)||NHC Key Laboratory of Human Disease Comparative Medicine||Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious||Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases||Tuberculosis Center, Chinese Academy of Medical Sciences (CAMS)
基础医学微生物学分子生物学
GPR183EBI2Mycobacterium tuberculosisRAW264.7BMDM
Tang Jun,Zhan Lingjun,Qin Chuan,Shi Ya?ˉnan.Downregulation of GPR183 on Infection Restricts the Early Infection and Intracellular Survival of Mycobacterium tuberculosis in Macrophage[EB/OL].(2025-03-28)[2025-06-19].https://www.biorxiv.org/content/10.1101/832592.点此复制
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