MAIT cells are activated during human viral infections

Bonnie van Wilgenburg(University of Oxford), Iris Scherwitzl(Hammersmith Hospital), Edward Hutchinson(University of Oxford), Tianqi Leng(University of Oxford), Ayako Kurioka(University of Oxford), Corinna A. Kulicke(University of Oxford), Catherine de Lara(University of Oxford), Suzanne Cole(University of Oxford), Sirijitt Vasanawathana(Khon Kaen University), Wannee Limpitikul(Songkhla Rajabhat University), Prida Malasit(National Science and Technology Development Agency), Duncan Young(John Radcliffe Hospital), Laura Denney(University of Oxford), Eleanor Barnes(University of Oxford), Jonathan K. Ball(University of Nottingham), Gary Burgess(Conatus Pharmaceuticals (United States)), G Cooke(Imperial College London), John Dillon(University of Dundee), Charles Gore(The Hepatitis C Trust), Graham R. Foster(Queen Mary University of London), Neil Guha(University of Nottingham), Rachel Halford(The Hepatitis C Trust), Cham Herath(Gilead Sciences (United Kingdom)), Christopher Holmes(University of Oxford), Anita Y. M. Howe(St. Paul's Hospital), Emma Hudson(University of Oxford), William L. Irving(University of Nottingham), Salim I. Khakoo(University of Southampton), Diana Koletzki(Janssen (Belgium)), Natasha K. Martin(University of California San Diego), Tamyo Mbisa(Public Health England), Jane A. McKeating(University of Birmingham), John McLauchlan(University of Glasgow), Alec Miners(London School of Hygiene & Tropical Medicine), Andrea Murray(Nottingham City Hospital), Peter Shaw(Merck & Co., Inc., Rahway, NJ, USA (United States)), Peter Simmonds(University of Oxford), Chris C. A. Spencer(Centre for Human Genetics), Paul Targett‐Adams(Medivir (Sweden)), Emma C. Thomson(University of Glasgow), Peter Vickerman(University of Bristol), Nicole Zitzmann(University of Oxford), Michael Moore(University of Oxford), Paolo Fabris(Ospedale San Bortolo), Maria Teresa Giordani(Ospedale San Bortolo), Ye Htun Oo(NIHR Birmingham Liver Biomedical Research Unit), Stephen M. Laidlaw(Nuffield Orthopaedic Centre), Lynn B. Dustin(Nuffield Orthopaedic Centre), Ling‐Pei Ho(University of Oxford), Fiona M. Thompson(University of Oxford), Narayan Ramamurthy(University of Oxford), Juthathip Mongkolsapaya(Siriraj Hospital), Christian B. Willberg(John Radcliffe Hospital), Gavin Screaton(Hammersmith Hospital), Paul Klenerman(John Radcliffe Hospital)
Nature Communications
June 23, 2016
10.1038/ncomms11653
Cited by 518Open Access
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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.

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