| First Author | Böhme J | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 5225 |
| PubMed ID | 33067434 | Mgi Jnum | J:298741 |
| Mgi Id | MGI:6470359 | Doi | 10.1038/s41467-020-19095-z |
| Citation | Bohme J, et al. (2020) Metformin enhances anti-mycobacterial responses by educating CD8+ T-cell immunometabolic circuits. Nat Commun 11(1):5225 |
| abstractText | Patients with type 2 diabetes (T2D) have a lower risk of Mycobacterium tuberculosis infection, progression from infection to tuberculosis (TB) disease, TB morality and TB recurrence, when being treated with metformin. However, a detailed mechanistic understanding of these protective effects is lacking. Here, we use mass cytometry to show that metformin treatment expands a population of memory-like antigen-inexperienced CD8(+)CXCR3(+) T cells in naive mice, and in healthy individuals and patients with T2D. Metformin-educated CD8(+) T cells have increased (i) mitochondrial mass, oxidative phosphorylation, and fatty acid oxidation; (ii) survival capacity; and (iii) anti-mycobacterial properties. CD8(+) T cells from Cxcr3(-/-) mice do not exhibit this metformin-mediated metabolic programming. In BCG-vaccinated mice and guinea pigs, metformin enhances immunogenicity and protective efficacy against M. tuberculosis challenge. Collectively, these results demonstrate an important function of CD8(+) T cells in metformin-derived host metabolic-fitness towards M. tuberculosis infection. |
