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

作者：Sangsu Bang, Christopher R. Donnelly, Xin Luo, Maria Toro-Moreno, Xueshu Tao, Zilong Wang, Sharat Chandra, Andrey V. Bortsov, Emily R. Derbyshire, Ru‐Rong Ji · 发表于：Nature Communications · 年份：2021 · DOI：10.1038/s41467-021-21940-8 · 被引用次数：96 · 研究领域：Neuropeptides and Animal Physiology、Receptor Mechanisms and Signaling、Drug Transport and Resistance Mechanisms

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.