MAIT cells are activated during human viral infections

Bonnie Van Wilgenburg (Lead / Corresponding author), Iris Scherwitzl, Edward C. Hutchinson, Tianqi Leng, Ayako Kurioka, Corinna Kulicke, Catherine De Lara, Suzanne Cole, Sirijitt Vasanawathana, Wannee Limpitikul, Prida Malasit, Duncan Young, Laura Denney, Michael D. Moore, Paolo Fabris, Maria Teresa Giordani, Ye Htun Oo, Stephen M. Laidlaw, Lynn B. Dustin, Ling Pei HoFiona M. Thompson, Narayan Ramamurthy, Juthathip Mongkolsapaya, Christian B. Willberg, Gavin R. Screaton, Paul Klenerman, Eleanor Barnes, Jonathan Ball, Gary Burgess, Graham Cooke, John Dillon, Charles Gore, Graham Foster, Neil Guha, Rachel Halford, Cham Herath, Chris Holmes, Anita Howe, Emma Hudson, William Irving, Salim Khakoo, Diana Koletzki, Natasha Martin, Tamyo Mbisa, Jane McKeating, John McLauchlan, Alec Miners, Andrea Murray, Peter Shaw, Peter Simmonds, Chris Spencer, Paul Targett-Adams, Emma Thomson, Peter Vickerman, Nicole Zitzmann

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Abstract

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.

Original languageEnglish
Article number11653
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 23 Jun 2016

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