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

Virulence

Fang Liu¹  Xinting Zhu²  Xiao-Fei Li²  Changwei Song³  Changyan Yu³  Ying Qin³  Sanhua Li³  Yi Xiao³  Nian Jiang³  Lingjie Meng³  Yun Liu³  Jing Hui³ 

[1] College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou, Chin;Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou, Chin;College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou, Chin;Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou, Chin;Research Center for Medicine & Biology, Zunyi Medical University, Zunyi, Guizhou, Chin;

关键词: Metformin;    innate immunity;    p38 MAPK pathway;    C. elegans;   

DOI  :  10.1080/21505594.2019.1706305

来源: Taylor & Francis

【 摘 要 】

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.

【 授权许可】

CC BY