Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation

Liyen Loh, Zhongfang Wang, Sneha Sant, Marios Koutsakos, Sinthujan Jegaskanda, Alexandra J. Corbett, Ligong Liu, David P. Fairlie, Jane Crowe, Jamie Rossjohn, Jianqing Xu, Peter C. Doherty, James McCluskey, Katherine Kedzierska

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes known to elicit potent immunity to a broad range of bacteria, mainly via the rapid production of inflammatory cytokines. Whether MAIT cells contribute to antiviral immunity is less clear. Here we asked whether MAIT cells produce cytokines/chemokines during severe human influenza virus infection. Our analysis in patients hospitalized with avian H7N9 influenza pneumonia showed that individuals who recovered had higher numbers of CD161+ Vα7.2+ MAIT cells in peripheral blood compared with those who succumbed, suggesting a possible protective role for this lymphocyte population. To understand the mechanism underlying MAIT cell activation during influenza, we cocultured influenza A virus (IAV)-infected human lung epithelial cells (A549) and human peripheral blood mononuclear cells in vitro, then assayed them by intracellular cytokine staining. Comparison of influenza-induced MAIT cell activation with the profile for natural killer cells (CD56+ CD3- ) showed robust up-regulation of IFNaγ for both cell populations and granzyme B in MAIT cells, although the individual responses varied among healthy donors. However, in contrast to the requirement for cell-associated factors to promote NK cell activation, the induction of MAIT cell cytokine production was dependent on IL-18 (but not IL-12) production by IAV-exposed CD14+ monocytes. Overall, this evidence for IAV activation via an indirect, IL-18-dependent mechanism indicates that MAIT cells are protective in influenza, and also possibly in any human disease process in which inflammation and IL-18 production occur.

Original languageEnglish
Pages (from-to)10133-10138
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume113
Issue number36
DOIs
Publication statusPublished - 6 Sep 2016

Keywords

  • H7N9
  • IL-18
  • Influenza virus
  • Mait cells
  • Monocytes

Cite this

Loh, Liyen ; Wang, Zhongfang ; Sant, Sneha ; Koutsakos, Marios ; Jegaskanda, Sinthujan ; Corbett, Alexandra J. ; Liu, Ligong ; Fairlie, David P. ; Crowe, Jane ; Rossjohn, Jamie ; Xu, Jianqing ; Doherty, Peter C. ; McCluskey, James ; Kedzierska, Katherine. / Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation. In: Proceedings of the National Academy of Sciences. 2016 ; Vol. 113, No. 36. pp. 10133-10138.
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title = "Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation",
abstract = "Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes known to elicit potent immunity to a broad range of bacteria, mainly via the rapid production of inflammatory cytokines. Whether MAIT cells contribute to antiviral immunity is less clear. Here we asked whether MAIT cells produce cytokines/chemokines during severe human influenza virus infection. Our analysis in patients hospitalized with avian H7N9 influenza pneumonia showed that individuals who recovered had higher numbers of CD161+ Vα7.2+ MAIT cells in peripheral blood compared with those who succumbed, suggesting a possible protective role for this lymphocyte population. To understand the mechanism underlying MAIT cell activation during influenza, we cocultured influenza A virus (IAV)-infected human lung epithelial cells (A549) and human peripheral blood mononuclear cells in vitro, then assayed them by intracellular cytokine staining. Comparison of influenza-induced MAIT cell activation with the profile for natural killer cells (CD56+ CD3- ) showed robust up-regulation of IFNaγ for both cell populations and granzyme B in MAIT cells, although the individual responses varied among healthy donors. However, in contrast to the requirement for cell-associated factors to promote NK cell activation, the induction of MAIT cell cytokine production was dependent on IL-18 (but not IL-12) production by IAV-exposed CD14+ monocytes. Overall, this evidence for IAV activation via an indirect, IL-18-dependent mechanism indicates that MAIT cells are protective in influenza, and also possibly in any human disease process in which inflammation and IL-18 production occur.",
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author = "Liyen Loh and Zhongfang Wang and Sneha Sant and Marios Koutsakos and Sinthujan Jegaskanda and Corbett, {Alexandra J.} and Ligong Liu and Fairlie, {David P.} and Jane Crowe and Jamie Rossjohn and Jianqing Xu and Doherty, {Peter C.} and James McCluskey and Katherine Kedzierska",
year = "2016",
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Loh, L, Wang, Z, Sant, S, Koutsakos, M, Jegaskanda, S, Corbett, AJ, Liu, L, Fairlie, DP, Crowe, J, Rossjohn, J, Xu, J, Doherty, PC, McCluskey, J & Kedzierska, K 2016, 'Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation' Proceedings of the National Academy of Sciences, vol. 113, no. 36, pp. 10133-10138. https://doi.org/10.1073/pnas.1610750113

Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation. / Loh, Liyen; Wang, Zhongfang; Sant, Sneha; Koutsakos, Marios; Jegaskanda, Sinthujan; Corbett, Alexandra J.; Liu, Ligong; Fairlie, David P.; Crowe, Jane; Rossjohn, Jamie; Xu, Jianqing; Doherty, Peter C.; McCluskey, James; Kedzierska, Katherine.

In: Proceedings of the National Academy of Sciences, Vol. 113, No. 36, 06.09.2016, p. 10133-10138.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Liu, Ligong

AU - Fairlie, David P.

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AU - Rossjohn, Jamie

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