UMMS Affiliation

Department of Medicine, Division of Pulmonary, Allergy And Critical Care Medicine

Publication Date

2020-10-16

Document Type

Article

Disciplines

Bacterial Infections and Mycoses | Immunology and Infectious Disease

Abstract

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.

Keywords

CD8-positive T cells, Immunological memory, Tuberculosis, Type 2 diabetes

Rights and Permissions

Copyright © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41467-020-19095-z

Source

Böhme J, Martinez N, Li S, Lee A, Marzuki M, Tizazu AM, Ackart D, Frenkel JH, Todd A, Lachmandas E, Lum J, Shihui F, Ng TP, Lee B, Larbi A, Netea MG, Basaraba R, van Crevel R, Newell E, Kornfeld H, Singhal A. Metformin enhances anti-mycobacterial responses by educating CD8+ T-cell immunometabolic circuits. Nat Commun. 2020 Oct 16;11(1):5225. doi: 10.1038/s41467-020-19095-z. PMID: 33067434; PMCID: PMC7567856. Link to article on publisher's site

Journal/Book/Conference Title

Nature communications

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

33067434

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Share

COinS