MAIT cells are activated during human viral infections

Bonnie Van Wilgenburg; Iris Scherwitzl; Edward C. Hutchinson; Tianqi Leng; Ayako Kurioka; Corinna Kulicke; Catherine De Lara; Suzanne Cole; Sirijitt Vasanawathana; Wannee Limpitikul; Prida Malasit; Duncan Young; Laura Denney; Michael D. Moore; Paolo Fabris; Maria Teresa Giordani; Ye Htun Oo; Stephen M. Laidlaw; Lynn B. Dustin; Ling Pei Ho; Fiona M. Thompson; Narayan Ramamurthy; Juthathip Mongkolsapaya; Christian B. Willberg; Gavin R. Screaton; Paul Klenerman; Eleanor Barnes; Jonathan Ball; Gary Burgess; Graham Cooke; John Dillon; Charles Gore; Graham Foster; Neil Guha; Rachel Halford; Cham Herath; Chris Holmes; Anita Howe; Emma Hudson; William Irving; Salim Khakoo; Diana Koletzki; Natasha Martin; Tamyo Mbisa; Jane McKeating; John McLauchlan; Alec Miners; Andrea Murray; Peter Shaw; Peter Simmonds; Chris Spencer; Paul Targett-Adams; Emma Thomson; Peter Vickerman; Nicole Zitzmann

doi:10.1038/ncomms11653

MAIT cells are activated during human viral infections

Bonnie Van Wilgenburg^*, Iris Scherwitzl, Edward C. Hutchinson, Tianqi Leng, Ayako Kurioka, Corinna Kulicke, Catherine De Lara, Suzanne Cole, Sirijitt Vasanawathana, Wannee Limpitikul, Prida Malasit, Duncan Young, Laura Denney, Michael D. Moore, Paolo Fabris, Maria Teresa Giordani, Ye Htun Oo, Stephen M. Laidlaw, Lynn B. Dustin, Ling Pei HoFiona M. Thompson, Narayan Ramamurthy, Juthathip Mongkolsapaya, Christian B. Willberg, Gavin R. Screaton, Paul Klenerman, Eleanor Barnes, Jonathan Ball, Gary Burgess, Graham Cooke, John Dillon, Charles Gore, Graham Foster, Neil Guha, Rachel Halford, Cham Herath, Chris Holmes, Anita Howe, Emma Hudson, William Irving, Salim Khakoo, Diana Koletzki, Natasha Martin, Tamyo Mbisa, Jane McKeating, John McLauchlan, Alec Miners, Andrea Murray, Peter Shaw, Peter Simmonds, Chris Spencer, Paul Targett-Adams, Emma Thomson, Peter Vickerman, Nicole Zitzmann

^*Corresponding author for this work

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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.

Original language	English
Article number	11653
Number of pages	11
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11653
Publication status	Published - 23 Jun 2016

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Van Wilgenburg, B., Scherwitzl, I., Hutchinson, E. C., Leng, T., Kurioka, A., Kulicke, C., De Lara, C., Cole, S., Vasanawathana, S., Limpitikul, W., Malasit, P., Young, D., Denney, L., Moore, M. D., Fabris, P., Giordani, M. T., Oo, Y. H., Laidlaw, S. M., Dustin, L. B., ... Zitzmann, N. (2016). MAIT cells are activated during human viral infections. Nature Communications, 7, Article 11653. https://doi.org/10.1038/ncomms11653

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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.",

author = "{Van Wilgenburg}, Bonnie and Iris Scherwitzl and Hutchinson, {Edward C.} and Tianqi Leng and Ayako Kurioka and Corinna Kulicke and {De Lara}, Catherine and Suzanne Cole and Sirijitt Vasanawathana and Wannee Limpitikul and Prida Malasit and Duncan Young and Laura Denney and Moore, {Michael D.} and Paolo Fabris and Giordani, {Maria Teresa} and Oo, {Ye Htun} and Laidlaw, {Stephen M.} and Dustin, {Lynn B.} and Ho, {Ling Pei} and Thompson, {Fiona M.} and Narayan Ramamurthy and Juthathip Mongkolsapaya and Willberg, {Christian B.} and Screaton, {Gavin R.} and Paul Klenerman and Eleanor Barnes and Jonathan Ball and Gary Burgess and Graham Cooke and John Dillon and Charles Gore and Graham Foster and Neil Guha and Rachel Halford and Cham Herath and Chris Holmes and Anita Howe and Emma Hudson and William Irving and Salim Khakoo and Diana Koletzki and Natasha Martin and Tamyo Mbisa and Jane McKeating and John McLauchlan and Alec Miners and Andrea Murray and Peter Shaw and Peter Simmonds and Chris Spencer and Paul Targett-Adams and Emma Thomson and Peter Vickerman and Nicole Zitzmann",

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Van Wilgenburg, B, Scherwitzl, I, Hutchinson, EC, Leng, T, Kurioka, A, Kulicke, C, De Lara, C, Cole, S, Vasanawathana, S, Limpitikul, W, Malasit, P, Young, D, Denney, L, Moore, MD, Fabris, P, Giordani, MT, Oo, YH, Laidlaw, SM, Dustin, LB, Ho, LP, Thompson, FM, Ramamurthy, N, Mongkolsapaya, J, Willberg, CB, Screaton, GR, Klenerman, P, Barnes, E, Ball, J, Burgess, G, Cooke, G, Dillon, J, Gore, C, Foster, G, Guha, N, Halford, R, Herath, C, Holmes, C, Howe, A, Hudson, E, Irving, W, Khakoo, S, Koletzki, D, Martin, N, Mbisa, T, McKeating, J, McLauchlan, J, Miners, A, Murray, A, Shaw, P, Simmonds, P, Spencer, C, Targett-Adams, P, Thomson, E, Vickerman, P & Zitzmann, N 2016, 'MAIT cells are activated during human viral infections', Nature Communications, vol. 7, 11653. https://doi.org/10.1038/ncomms11653

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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 Htun

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 - Barnes, Eleanor

AU - Ball, Jonathan

AU - Burgess, Gary

AU - Cooke, Graham

AU - Dillon, John

AU - Gore, Charles

AU - Foster, Graham

AU - Guha, Neil

AU - Halford, Rachel

AU - Herath, Cham

AU - Holmes, Chris

AU - Howe, Anita

AU - Hudson, Emma

AU - Irving, William

AU - Khakoo, Salim

AU - Koletzki, Diana

AU - Martin, Natasha

AU - Mbisa, Tamyo

AU - McKeating, Jane

AU - McLauchlan, John

AU - Miners, Alec

AU - Murray, Andrea

AU - Shaw, Peter

AU - Simmonds, Peter

AU - Spencer, Chris

AU - Targett-Adams, Paul

AU - Thomson, Emma

AU - Vickerman, Peter

AU - Zitzmann, Nicole

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.

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U2 - 10.1038/ncomms11653

DO - 10.1038/ncomms11653

M3 - Article (Academic Journal)

C2 - 27337592

AN - SCOPUS:84975705227

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11653

ER -

MAIT cells are activated during human viral infections

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