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Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice.

ABSTRACT: GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37^-/- mice. Notably, we found that ARU binds to GPR37 in macrophages and promotes phagocytosis and clearance of pathogens. Moreover, ablation of macrophages potentiated infection, sepsis, and their sequelae, whereas adoptive transfer of NPD1- or ARU-primed macrophages reduced infection, sepsis, and pain-like behaviors. Our findings reveal physiological actions of ARU in host cells by activating macrophages and suggest that GPR37 agonists may help to treat sepsis, bacterial infections, and malaria.

SUBMITTER: Bang S

PROVIDER: S-EPMC7969930 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice.

Bang Sangsu S Donnelly Christopher R CR Luo Xin X Toro-Moreno Maria M Tao Xueshu X Wang Zilong Z Chandra Sharat S Bortsov Andrey V AV Derbyshire Emily R ER Ji Ru-Rong RR

Nature communications 20210317 1

GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the prot ...[more]

PMID: 33731716

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Dataset Information

Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice.

Publications

Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice.

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