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.

使用二甲双胍治疗时，2 型糖尿病 (T2D) 患者的结核分枝杆菌感染、从感染进展为结核病 (TB) 疾病、结核病道德和结核病复发的风险较低。然而，缺乏对这些保护作用的详细机制理解。在这里，我们使用质谱流式技术证明，二甲双胍治疗可扩大初始小鼠、健康个体和 T2D 患者中记忆样抗原未经历过的 CD8 ⁺ CXCR3 ⁺ T 细胞群体。二甲双胍训练的 CD8 ⁺ T 细胞增加了 (i) 线粒体质量、氧化磷酸化和脂肪酸氧化； (ii) 生存能力； (iii) 抗分枝杆菌特性。来自Cxcr3 ^−/−小鼠的 CD8 ⁺ T 细胞不表现出这种二甲双胍介导的代谢程序。在接种卡介苗的小鼠和豚鼠中，二甲双胍增强了免疫原性和针对结核分枝杆菌攻击的保护功效。总的来说，这些结果证明了 CD8 ⁺ T 细胞在二甲双胍衍生的宿主针对结核分枝杆菌感染的代谢适应性中发挥着重要作用。