Background: 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.  As a mechanism for TCR-independent triggering of MAIT cells, we explored the contribution of cytokines. In particular Type I interferons, considering these classic anti-viral cytokines are readily induced in response to viruses.

Results: We found both in vitro and in vivo activation of MAIT cells in response to type I interferons. IFN-α/β in combination with IL-15 and IL-18 activated MAIT cell in vitro. We established in vitro models for viral infections using human CD8+ T cells, co-incubated with infected macrophages. MAIT cells were readily and specifically activated in response to Hepatitis C virus (HCV), as indicated by upregulation of IFN-γ and expression of and Granzyme B. In vitro blockade of type I interferons impacted on MAIT cell activation by HCV. Specific addition of IFN-α during HCV therapy, correlated with MAIT cell activation in vivo.

Conclusions: These data demonstrate that type I Interferons can contribute to MAIT cell activation in vitro and in vivo. We extended this finding by exploring MAIT cell responses to a range of other viruses and found consistent MAIT cell activation in the context of both DNA and RNA viral sensing, with varying patterns of triggering in each case. We conclude that activation by virus infection is a consistent feature of MAIT cell biology, with the potential for both immune protection and immunopathology.