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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: Xiao, Yi, Liu, Fang, Li, Sanhua, Jiang, Nian, Yu, Changyan, Zhu, Xinting, Qin, Ying, Hui, Jing, Meng, Lingjie, Song, Changwei, Li, Xiao-Fei, Liu, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961722/
https://www.ncbi.nlm.nih.gov/pubmed/31851866
http://dx.doi.org/10.1080/21505594.2019.1706305
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author Xiao, Yi
Liu, Fang
Li, Sanhua
Jiang, Nian
Yu, Changyan
Zhu, Xinting
Qin, Ying
Hui, Jing
Meng, Lingjie
Song, Changwei
Li, Xiao-Fei
Liu, Yun
author_facet Xiao, Yi
Liu, Fang
Li, Sanhua
Jiang, Nian
Yu, Changyan
Zhu, Xinting
Qin, Ying
Hui, Jing
Meng, Lingjie
Song, Changwei
Li, Xiao-Fei
Liu, Yun
author_sort Xiao, Yi
collection PubMed
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.
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spelling pubmed-69617222020-01-28 Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway Xiao, Yi Liu, Fang Li, Sanhua Jiang, Nian Yu, Changyan Zhu, Xinting Qin, Ying Hui, Jing Meng, Lingjie Song, Changwei Li, Xiao-Fei Liu, Yun Virulence Research Paper 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. Taylor & Francis 2019-12-28 /pmc/articles/PMC6961722/ /pubmed/31851866 http://dx.doi.org/10.1080/21505594.2019.1706305 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Xiao, Yi
Liu, Fang
Li, Sanhua
Jiang, Nian
Yu, Changyan
Zhu, Xinting
Qin, Ying
Hui, Jing
Meng, Lingjie
Song, Changwei
Li, Xiao-Fei
Liu, Yun
Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway
title 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_short 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
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961722/
https://www.ncbi.nlm.nih.gov/pubmed/31851866
http://dx.doi.org/10.1080/21505594.2019.1706305
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