Mucosal-associated invariant T (MAIT) cells are potential targets of vaccination and host-directed therapeutics for tuberculosis, but the role of MAIT cells during Mycobacterium tuberculosis (Mtb) infection in vivo is not well understood. Here we find that following Mtb infection MAIT cells mount minimal responses, and MAIT cell-deficient MR1^−/− mice display normal survival. Preinfection expansion of MAIT cells through 5-OP-RU vaccination fails to protect against subsequent Mtb challenge. In fact, 5-OP-RU vaccination delays Mtb-specific CD4 T cell priming in lung-draining lymph nodes, and conversely MR1 deficiency or blockade accelerates T cell priming. The MAIT cell-mediated delay in T cell priming is partly dependent on TGF-β. Surprisingly, 5-OP-RU treatment during chronic infection drives MAIT cell expansion and an IL-17A-dependent reduction in bacterial loads. Thus, during early infection MAIT cells directly contribute to the notoriously slow priming of CD4 T cells, but later during infection MAIT cell stimulation may be an effective host-directed therapy for tuberculosis.

粘膜相关不变 T (MAIT) 细胞是结核病疫苗接种和宿主定向治疗的潜在目标，但 MAIT 细胞在结核分枝杆菌(Mtb) 体内感染期间的作用尚不清楚。在这里，我们发现 Mtb 感染后 MAIT 细胞产生最小反应，而 MAIT 细胞缺陷型 MR1 ^-/-小鼠显示正常存活。通过 5-OP-RU 疫苗接种 MAIT 细胞的感染前扩增无法防止随后的 Mtb 攻击。事实上，5-OP-RU 疫苗接种会延迟肺引流淋巴结中 Mtb 特异性 CD4 T 细胞的启动，相反，MR1 缺乏或阻断会加速 T 细胞启动。MAIT 细胞介导的 T 细胞启动延迟部分取决于 TGF-β。令人惊讶的是，慢性感染期间的 5-OP-RU 治疗可驱动 MAIT 细胞扩增和依赖于 IL-17A 的细菌负荷减少。因此，在早期感染期间，MAIT 细胞直接导致众所周知的 CD4 T 细胞启动缓慢，但在感染后期，MAIT 细胞刺激可能是一种有效的宿主导向治疗结核病的方法。