title: MAIT cells are activated during human viral infections.
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.
authors.affiliation: Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Bonnie
authors.identifier: 0000-0002-0038-584X
authors.initials: B
authors.lastname: van Wilgenburg
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College, Hammersmith Campus, London W12 0NN, UK.
authors.forename: Iris
authors.initials: I
authors.lastname: Scherwitzl
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Edward C
authors.identifier: 0000-0003-3673-9096
authors.initials: EC
authors.lastname: Hutchinson
authors.affiliation: Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Tianqi
authors.initials: T
authors.lastname: Leng
authors.affiliation: Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kurioka
authors.affiliation: Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Corinna
authors.initials: C
authors.lastname: Kulicke
authors.affiliation: Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: de Lara
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Cole
authors.affiliation: Department of Pediatric, Khon Kaen Hospital, Khon Kaen 40000, Thailand.
authors.forename: Sirijitt
authors.initials: S
authors.lastname: Vasanawathana
authors.affiliation: Department of Pediatric, Songkhla Hospital, Songkhla 90100, Thailand.
authors.forename: Wannee
authors.initials: W
authors.lastname: Limpitikul
authors.affiliation: BIOTEC, NSTDA, Phatumthani 12120, Thailand.|Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Prida
authors.initials: P
authors.lastname: Malasit
authors.affiliation: Nuffield Department of Anesthesia, The John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: Duncan
authors.initials: D
authors.lastname: Young
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Denney
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Moore
authors.affiliation: Infectious Diseases and Tropical Medicine Unit, San Bortolo Hospital, Vicenza, VI 37, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fabris
authors.affiliation: Infectious Diseases and Tropical Medicine Unit, San Bortolo Hospital, Vicenza, VI 37, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Giordani
authors.affiliation: Centre for Liver Research &NIHR Biomedical Research Unit in Liver Disease, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Ye Htun
authors.initials: YH
authors.lastname: Oo
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7 LF, UK.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Laidlaw
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7 LF, UK.
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Dustin
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Ling-Pei
authors.initials: LP
authors.lastname: Ho
authors.affiliation: Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Thompson
authors.affiliation: Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Narayan
authors.initials: N
authors.lastname: Ramamurthy
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College, Hammersmith Campus, London W12 0NN, UK.|Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Juthathip
authors.initials: J
authors.lastname: Mongkolsapaya
authors.affiliation: Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 3SY, UK.|Oxford NIHR Biomedical Research Centre, The John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: Christian B
authors.identifier: 0000-0001-5299-9344
authors.initials: CB
authors.lastname: Willberg
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College, Hammersmith Campus, London W12 0NN, UK.
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Screaton
authors.affiliation: Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 3SY, UK.|Oxford NIHR Biomedical Research Centre, The John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: Paul
authors.identifier: 0000-0003-4307-9161
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D000072336:Mucosal-Associated Invariant T Cells / Q000502:physiology*; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D016207:Cytokines