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Nat Commun. 2016 Jun 23;7:11653. doi: 10.1038/ncomms11653.

MAIT cells are activated during human viral infections.

Author information

1
Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 3SY, UK.
2
Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College, Hammersmith Campus, London W12 0NN, UK.
3
Sir William Dunn School of Pathology, University of Oxford, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
4
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 9DU, UK.
5
Department of Pediatric, Khon Kaen Hospital, Khon Kaen 40000, Thailand.
6
Department of Pediatric, Songkhla Hospital, Songkhla 90100, Thailand.
7
BIOTEC, NSTDA, Phatumthani 12120, Thailand.
8
Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
9
Nuffield Department of Anesthesia, The John Radcliffe Hospital, Oxford OX3 9DU, UK.
10
Infectious Diseases and Tropical Medicine Unit, San Bortolo Hospital, Vicenza, VI 37, Italy.
11
Centre for Liver Research &NIHR Biomedical Research Unit in Liver Disease, University of Birmingham, Birmingham B15 2TT, UK.
12
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7 LF, UK.
13
Oxford NIHR Biomedical Research Centre, The John Radcliffe Hospital, Oxford OX3 9DU, UK.

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.

PMID:
27337592
PMCID:
PMC4931007
DOI:
10.1038/ncomms11653
[Indexed for MEDLINE]
Free PMC Article

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