Metformin enhances anti-mycobacterial responses by educating immunometabolic circuits of CD8+ T cells
Tze Pin Ng,
Reinout van Crevel,
Evan W Newell,
Posted 27 Aug 2020
bioRxiv DOI: 10.1101/2020.08.26.269217 (published DOI: 10.1038/s41467-020-19095-z)
Posted 27 Aug 2020
Diabetic patients taking metformin have lower risk for Mycobacterium tuberculosis (Mtb) infection, progression from infection to tuberculosis (TB) disease, TB morality and TB recurrence. However, a detailed mechanistic understanding of metformins protective immunological benefits on host resistance to TB is lacking. In this study, using mass cytometry we show that metformin treatment expands memory-like antigen-inexperienced CD8+CXCR3+ T cells in naive mice, and in healthy and diabetic humans. Metformin-educated CD8+ T cells have increased (1) mitochondrial mass, oxidative phosphorylation, and fatty acid oxidation; (2) survival capacity; and (3) anti-mycobacterial properties. CD8+ T cells from CXCR3-/- mice did not exhibit metformin-mediated metabolic programming. In BCG-vaccinated mice and guinea pigs, metformin enhanced immunogenicity and protective efficacy against Mtb challenge. Collectively, our results demonstrate an important role of CD8+ T cells in metformin-derived host metabolic-fitness towards Mtb infection. ### Competing Interest Statement The authors have declared no competing interest.
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