The Peter Gorer Department of Immunobiology, King's College London, London, UK.
The Francis Crick Institute , London, UK.
J Exp Med. 2023 Oct 2;220(10). doi: 10.1084/jem.20230037. Epub 2023 Jul 26.
Mucosal-associated invariant T (MAIT) cells are abundant in the lung and contribute to host defense against infections. During bacterial infections, MAIT cell activation has been proposed to require T cell receptor (TCR)-mediated recognition of antigens derived from the riboflavin synthesis pathway presented by the antigen-presenting molecule MR1. MAIT cells can also be activated by cytokines in an MR1-independent manner, yet the contribution of MR1-dependent vs. -independent signals to MAIT cell functions in vivo remains unclear. Here, we use Klebsiella pneumoniae as a model of bacterial pneumonia and demonstrate that MAIT cell activation is independent of MR1 and primarily driven by type I interferons (IFNs). During Klebsiella infection, type I IFNs stimulate activation of murine and human MAIT cells, induce a Th1/cytotoxic transcriptional program, and modulate MAIT cell location within the lungs. Consequently, adoptive transfer or boosting of pulmonary MAIT cells protect mice from Klebsiella infection, with protection being dependent on direct type I IFN signaling on MAIT cells. These findings reveal type I IFNs as new molecular targets to manipulate MAIT cell functions during bacterial infections.
黏膜相关不变 T（MAIT）细胞在肺部丰富，并有助于宿主防御感染。在细菌感染期间，已经提出 MAIT 细胞的激活需要 T 细胞受体（TCR）介导的对由呈递分子 MR1 呈现的来自核黄素合成途径的抗原的识别。MAIT 细胞也可以通过 MR1 非依赖性方式被细胞因子激活，但是 MR1 依赖性与非依赖性信号对 MAIT 细胞在体内功能的贡献仍然不清楚。在这里，我们使用肺炎克雷伯菌作为细菌性肺炎的模型，并证明 MAIT 细胞的激活不依赖于 MR1，主要由 I 型干扰素（IFN）驱动。在肺炎克雷伯菌感染期间，I 型 IFNs 刺激鼠和人 MAIT 细胞的激活，诱导 Th1/细胞毒性转录程序，并调节 MAIT 细胞在肺部中的位置。因此，肺 MAIT 细胞的过继转移或增强可保护小鼠免受肺炎克雷伯菌感染，而保护作用依赖于 MAIT 细胞上的直接 I 型 IFN 信号。这些发现揭示了 I 型 IFNs 作为新的分子靶点，可在细菌感染期间操纵 MAIT 细胞的功能。
