Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway

Metformin, as the first-line oral drug for type 2 diabetes, has proven benefits against aging, cancer and cardiovascular diseases. But the influence of metformin to the immune response and its molecular mechanisms remain obscure. Metformin increases resistance to not only the Gram-negative pathogens...

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Autores principales:	Yi Xiao, Fang Liu, Sanhua Li, Nian Jiang, Changyan Yu, Xinting Zhu, Ying Qin, Jing Hui, Lingjie Meng, Changwei Song, Xiao-Fei Li, Yun Liu
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	metformin innate immunity p38 mapk pathway c. elegans Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/ce01c8a67b434c479938e84cc840fcfc
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spelling	oai:doaj.org-article:ce01c8a67b434c479938e84cc840fcfc2021-11-17T14:21:57ZMetformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway2150-55942150-560810.1080/21505594.2019.1706305https://doaj.org/article/ce01c8a67b434c479938e84cc840fcfc2020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2019.1706305https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Metformin, as the first-line oral drug for type 2 diabetes, has proven benefits against aging, cancer and cardiovascular diseases. But the influence of metformin to the immune response and its molecular mechanisms remain obscure. Metformin increases resistance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus. Meanwhile, metformin protects the animals from the infection by enhancing the tolerance to the pathogen infection rather than by reducing the bacterial burden. Through the screening of classical immune pathways in C. elegans, we find metformin enhances innate immunity through p38 MAPK pathway. Furthermore, activated p38/PMK-1 by metformin acts on the intestine for innate immune response. In addition, metformin-treated mice have increased resistance to P. aeruginosa PA14 infection and significantly increased the levels of active PMK-1. Therefore, promoted p38/PMK-1-mediated innate immunity by metformin is conserved from worms to mammals. Our work provides a conserved mechanism by which metformin enhances immune response and boosts its therapeutic application in the treatment of pathogen infection.Yi XiaoFang LiuSanhua LiNian JiangChangyan YuXinting ZhuYing QinJing HuiLingjie MengChangwei SongXiao-Fei LiYun LiuTaylor & Francis Grouparticlemetformininnate immunityp38 mapk pathwayc. elegansInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 39-48 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	metformin innate immunity p38 mapk pathway c. elegans Infectious and parasitic diseases RC109-216
spellingShingle	metformin innate immunity p38 mapk pathway c. elegans Infectious and parasitic diseases RC109-216 Yi Xiao Fang Liu Sanhua Li Nian Jiang Changyan Yu Xinting Zhu Ying Qin Jing Hui Lingjie Meng Changwei Song Xiao-Fei Li Yun Liu Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway
description	Metformin, as the first-line oral drug for type 2 diabetes, has proven benefits against aging, cancer and cardiovascular diseases. But the influence of metformin to the immune response and its molecular mechanisms remain obscure. Metformin increases resistance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus. Meanwhile, metformin protects the animals from the infection by enhancing the tolerance to the pathogen infection rather than by reducing the bacterial burden. Through the screening of classical immune pathways in C. elegans, we find metformin enhances innate immunity through p38 MAPK pathway. Furthermore, activated p38/PMK-1 by metformin acts on the intestine for innate immune response. In addition, metformin-treated mice have increased resistance to P. aeruginosa PA14 infection and significantly increased the levels of active PMK-1. Therefore, promoted p38/PMK-1-mediated innate immunity by metformin is conserved from worms to mammals. Our work provides a conserved mechanism by which metformin enhances immune response and boosts its therapeutic application in the treatment of pathogen infection.
format	article
author	Yi Xiao Fang Liu Sanhua Li Nian Jiang Changyan Yu Xinting Zhu Ying Qin Jing Hui Lingjie Meng Changwei Song Xiao-Fei Li Yun Liu
author_facet	Yi Xiao Fang Liu Sanhua Li Nian Jiang Changyan Yu Xinting Zhu Ying Qin Jing Hui Lingjie Meng Changwei Song Xiao-Fei Li Yun Liu
author_sort	Yi Xiao
title	Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway
title_short	Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway
title_full	Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway
title_fullStr	Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway
title_full_unstemmed	Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway
title_sort	metformin promotes innate immunity through a conserved pmk-1/p38 mapk pathway
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/ce01c8a67b434c479938e84cc840fcfc
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Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway

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