Enhancement of antimalarial immune memory by metformin and elucidation of its mechanism

Using a mouse malaria model, we analyzed whether the oral antidiabetic drug metformin enhances the activation of malaria parasite-specific T cells and the differentiation and maintenance of memory cells, and also the mechanism. Although malaria antigen-specific CD4+ T cells and CD8+ T cells increased on day 7 post infection and then decreased sharply, the differentiation of T cells into effector T cells and effector memory T cells was observed on day18 post-infection in mice treated with metformin. Also, metformin enhanced S6 phosphorylation but not AMPK phosphorylation on day18. These results suggest that metformin enhanced the differentiation, proliferation, and survival of effector T cells and effector memory T cells by promoting phosphorylation of S6 in T cells. 

Antimalarial drugs that directly kill the parasite are commercially available, but it is a cat-and-mouse game given that drug-resistant malaria parasites are emerging one after another. This study revealed that metformin promotes effector and effector memory T cell differentiation of antigen-specific T cells, as well as proliferation and survival, indicating that metformin can overcome the drug resistance and immune evasion of the parasite itself. This can be expected as a clue to the development of new treatments. Furthermore, since there is currently no malaria vaccine that is sufficiently effective, it is also expected to be applied to metformin combination therapy for the purpose of enhancing vaccine efficacy.

Project details

Basic Science

Apr 2019 — Mar 2023

$38,484

Japan