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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 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: 19 Oct 2019 07:40
URI: http://orca-mwe.cf.ac.uk/id/eprint/100014

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