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: 10133-10138. doi:10.1073/pnas.1610750113

Author 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
Title Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation
Journal name Proceedings of the National Academy of Sciences   Check publisher's open access policy
ISSN 1091-6490
Publication date 2016-09-06
Sub-type Article (original research)
DOI 10.1073/pnas.1610750113
Open Access Status Not yet assessed
Volume 113
Issue 36
Start page 10133
End page 10138
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Formatted 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.
Keyword H7N9
Influenza virus
MAIT cells
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 7 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 09 Oct 2016, 10:38:35 EST by System User on behalf of Learning and Research Services (UQ Library)