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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Bang, S; Donnelly, CR; Luo, X; Toro-Moreno, M; Tao, X; Wang, Z; Chandra, S; Bortsov, AV; Derbyshire, ER; Ji, R-R

Published Date

  • March 17, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 1704 -

PubMed ID

  • 33731716

Pubmed Central ID

  • PMC7969930

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-021-21940-8


  • eng

Conference Location

  • England