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Proc Natl Acad Sci U S A. 2016 Aug 19. pii: 201610750. [Epub ahead of print]
Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation.
Loh L1, Wang Z1, Sant S1, Koutsakos M1, Jegaskanda S2, Corbett AJ1, Liu L3, Fairlie DP3, Crowe J4, Rossjohn J5, Xu J6, Doherty PC7, McCluskey J1, Kedzierska K8.
Author information
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.
KEYWORDS:
H7N9; IL-18; MAIT cells; influenza virus; monocytes
PMID: 27543331 DOI: 10.1073/pnas.1610750113
[PubMed - as supplied by publisher] Free full text
Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation.
Loh L1, Wang Z1, Sant S1, Koutsakos M1, Jegaskanda S2, Corbett AJ1, Liu L3, Fairlie DP3, Crowe J4, Rossjohn J5, Xu J6, Doherty PC7, McCluskey J1, Kedzierska K8.
Author information
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.
KEYWORDS:
H7N9; IL-18; MAIT cells; influenza virus; monocytes
PMID: 27543331 DOI: 10.1073/pnas.1610750113
[PubMed - as supplied by publisher] Free full text