University of Oxford; Imperial College London; University of Oxford; University of Oxford; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); Mahidol University; University of Oxford; ULSS 8 Berica; Ospedale San Bortolo di Vicenza; University of Birmingham; University of Birmingham; University of Oxford; University of Oxford
Type
Article
Source Title
NATURE COMMUNICATIONS
Year
2016
Volume
7
Open Access
gold, Green Submitted, Green Published, Green Accepted
Publisher
NATURE PUBLISHING GROUP
DOI
10.1038/ncomms11653
Format
PDF
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-alpha/beta. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection. Furthermore, HCV treatment with interferon-alpha 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-gamma. Together these data demonstrate MAIT cells are activated following viral infections, and suggest a potential role in both host defence and immunopathology.
NIHR Biomedical Research Program (Oxford); Wellcome Trust [WT091663MA]; National Institutes for Health Research Biomedical Research Centre (Imperial College); NIH [U19AI082630]; Oxford Martin School; Wellcome Trust programme Grant [PS2186_WMII]; Medical Research Council; MRC programme Grant [MR/K000241/1]; MRC Project [G0600371]; MRC intermediate fellowship programme; MRC [G0400720, MC_PC_12020, MR/K010239/1, G0600371, MC_UU_12014/9, G1100247, G1002552, G0801508, MR/K01532X/1, MR/K000241/1] Funding Source: UKRI; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U19AI082630] Funding Source: NIH RePORTER; Medical Research Council [G0801508, G0600371, MR/K01532X/1, G1002552, MC_PC_12020, MR/K000241/1, MR/K010239/1, G0400720] Funding Source: researchfish; National Institute for Health Research [NF-SI-0515-10005] Funding Source: researchfish
