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 ORCID: https://orcid.org/0000-0002-2020-7522, Xu, Jianqing, Doherty, Peter C., McCluskey, James and Kedzierska, Katherine 2016. Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18–dependent activation. Proceedings of the National Academy of Sciences 113 (36) , pp. 10133-10138. 10.1073/pnas.1610750113

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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 IFNγ 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	National Academy of Sciences
ISSN:	0027-8424
Date of First Compliant Deposit:	20 September 2017
Last Modified:	20 Nov 2024 04:45
URI:	https://orca.cardiff.ac.uk/id/eprint/100014

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