TY - JOUR
T1 - MAIT cells are activated during human viral infections
AU - van Wilgenburg, Bonnie
AU - Scherwitzl, Iris
AU - Hutchinson, Edward C
AU - Leng, Tianqi
AU - Kurioka, Ayako
AU - Kulicke, Corinna
AU - de Lara, Catherine
AU - Cole, Suzanne
AU - Vasanawathana, Sirijitt
AU - Limpitikul, Wannee
AU - Malasit, Prida
AU - Young, Duncan
AU - Denney, Laura
AU - Moore, Michael D
AU - Fabris, Paolo
AU - Giordani, Maria Teresa
AU - Oo, Ye
AU - Laidlaw, Stephen M
AU - Dustin, Lynn B
AU - Ho, Ling-Pei
AU - Thompson, Fiona M
AU - Ramamurthy, Narayan
AU - Mongkolsapaya, Juthathip
AU - Willberg, Christian B
AU - Screaton, Gavin R
AU - Klenerman, Paul
AU - STOP-HCV consortium
PY - 2016/6/23
Y1 - 2016/6/23
N2 - 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.
AB - 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.
U2 - 10.1038/ncomms11653
DO - 10.1038/ncomms11653
M3 - Article
C2 - 27337592
SN - 2041-1723
VL - 7
JO - Nature Communications
JF - Nature Communications
M1 - 11653
ER -