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Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice
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)...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969930/ https://www.ncbi.nlm.nih.gov/pubmed/33731716 http://dx.doi.org/10.1038/s41467-021-21940-8 |
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author | Bang, Sangsu Donnelly, Christopher R. Luo, Xin Toro-Moreno, Maria Tao, Xueshu Wang, Zilong Chandra, Sharat Bortsov, Andrey V. Derbyshire, Emily R. Ji, Ru-Rong |
author_facet | Bang, Sangsu Donnelly, Christopher R. Luo, Xin Toro-Moreno, Maria Tao, Xueshu Wang, Zilong Chandra, Sharat Bortsov, Andrey V. Derbyshire, Emily R. Ji, Ru-Rong |
author_sort | Bang, Sangsu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7969930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79699302021-04-16 Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice Bang, Sangsu Donnelly, Christopher R. Luo, Xin Toro-Moreno, Maria Tao, Xueshu Wang, Zilong Chandra, Sharat Bortsov, Andrey V. Derbyshire, Emily R. Ji, Ru-Rong Nat Commun 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. Nature Publishing Group UK 2021-03-17 /pmc/articles/PMC7969930/ /pubmed/33731716 http://dx.doi.org/10.1038/s41467-021-21940-8 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Bang, Sangsu Donnelly, Christopher R. Luo, Xin Toro-Moreno, Maria Tao, Xueshu Wang, Zilong Chandra, Sharat Bortsov, Andrey V. Derbyshire, Emily R. Ji, Ru-Rong Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice |
title | Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice |
title_full | Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice |
title_fullStr | Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice |
title_full_unstemmed | Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice |
title_short | Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice |
title_sort | activation of gpr37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969930/ https://www.ncbi.nlm.nih.gov/pubmed/33731716 http://dx.doi.org/10.1038/s41467-021-21940-8 |
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