Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 3SY, UK.
Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College, Hammersmith Campus, London W12 0NN, UK.
Nat Commun. 2016 Jun 23;7:11653. doi: 10.1038/ncomms11653.
Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus. This activation-driving cytokine release and Granzyme B upregulation-is TCR-independent but dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-α/β. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection. Furthermore, HCV treatment with interferon-α leads to specific MAIT cell activation in vivo in parallel with an enhanced therapeutic response. Moreover, TCR-independent activation of MAIT cells leads to a reduction of HCV replication in vitro mediated by IFN-γ. Together these data demonstrate MAIT cells are activated following viral infections, and suggest a potential role in both host defence and immunopathology.
黏膜相关恒定 T（MAIT）细胞在人类中丰富存在，并能识别细菌配体。在这里，我们证明 MAIT 细胞在人类病毒感染过程中也会被激活。在感染登革热病毒、丙型肝炎病毒和流感病毒时观察到 MAIT 细胞的激活。这种激活驱动细胞因子释放和颗粒酶 B 的上调，与 TCR 无关，但与 IL-18 协同作用，IL-12、IL-15 和/或干扰素-α/β也发挥作用。IL-18 水平和 MAIT 细胞的激活与急性登革热感染的疾病严重程度相关。此外，用干扰素-α治疗丙型肝炎病毒会导致体内特定的 MAIT 细胞激活，同时增强治疗反应。此外，MAIT 细胞的 TCR 非依赖性激活会导致体外丙型肝炎病毒复制减少，这一过程由 IFN-γ介导。这些数据共同表明，MAIT 细胞在病毒感染后被激活，并提示其在宿主防御和免疫病理学中可能发挥作用。
