Human MAIT cells respond to virus infection

Mucosal Associated Invariant T (MAIT) cells are an abundant population of tissue homing T-cells, possessing TCRs capable of recognising bacterially-derived riboflavin synthesis intermediates. However, their ability to respond to viral pathogens has not been defined. We addressed whether human MAIT cell populations responded to viral infections in vivo and the mechanism behind this. We find consistent evidence for MAIT cell activation during infection with Dengue virus, Hepatitis C virus (HCV), and Influenza Virus. This activation – driving cytokine release and upregulation of Granzyme B – was TCR-independent but dependent on specific cytokines, notably IL-18 in synergy with IL-12, IL-15 and/or type I interferons. IL-18 levels and activation of MAIT cells correlated with disease severity in acute Dengue infection. Furthermore, treatment of HCV with interferon-α led to specific activation of MAIT cells in vivo. Together these data demonstrate MAIT cells as virally-responsive and suggest a role in both host defence and immunopathology.