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 language | English |
|---|---|
| Pages (from-to) | 10133-10138 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences |
| Volume | 113 |
| Issue number | 36 |
| DOIs | |
| Publication status | Published - 6 Sep 2016 |
Keywords
- H7N9
- IL-18
- Influenza virus
- Mait cells
- Monocytes
Cite this
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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; Kedzierska, Katherine.
In: Proceedings of the National Academy of Sciences, Vol. 113, No. 36, 06.09.2016, p. 10133-10138.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation
AU - Loh, Liyen
AU - Wang, Zhongfang
AU - Sant, Sneha
AU - Koutsakos, Marios
AU - Jegaskanda, Sinthujan
AU - Corbett, Alexandra J.
AU - Liu, Ligong
AU - Fairlie, David P.
AU - Crowe, Jane
AU - Rossjohn, Jamie
AU - Xu, Jianqing
AU - Doherty, Peter C.
AU - McCluskey, James
AU - Kedzierska, Katherine
PY - 2016/9/6
Y1 - 2016/9/6
N2 - 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.
AB - 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.
KW - H7N9
KW - IL-18
KW - Influenza virus
KW - Mait cells
KW - Monocytes
UR - http://www.scopus.com/inward/record.url?scp=84985910577&partnerID=8YFLogxK
U2 - 10.1073/pnas.1610750113
DO - 10.1073/pnas.1610750113
M3 - Article
VL - 113
SP - 10133
EP - 10138
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 36
ER -