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: | 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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