tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A. 2016 Aug 19. pii: 201610750. [Epub ahead of print]
[h=1]Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation.[/h] Loh L[SUP]1[/SUP], Wang Z[SUP]1[/SUP], Sant S[SUP]1[/SUP], Koutsakos M[SUP]1[/SUP], Jegaskanda S[SUP]2[/SUP], Corbett AJ[SUP]1[/SUP], Liu L[SUP]3[/SUP], Fairlie DP[SUP]3[/SUP], Crowe J[SUP]4[/SUP], Rossjohn J[SUP]5[/SUP], Xu J[SUP]6[/SUP], Doherty PC[SUP]7[/SUP], McCluskey J[SUP]1[/SUP], Kedzierska K[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+[/SUP]Vα7.2[SUP]+[/SUP] 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[SUP]+[/SUP]CD3[SUP]-[/SUP]) 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[SUP]+[/SUP] 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.
[h=4]KEYWORDS:[/h] H7N9; IL-18; MAIT cells; influenza virus; monocytes
PMID: 27543331 DOI: 10.1073/pnas.1610750113
[PubMed - as supplied by publisher] Free full text
[h=1]Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation.[/h] Loh L[SUP]1[/SUP], Wang Z[SUP]1[/SUP], Sant S[SUP]1[/SUP], Koutsakos M[SUP]1[/SUP], Jegaskanda S[SUP]2[/SUP], Corbett AJ[SUP]1[/SUP], Liu L[SUP]3[/SUP], Fairlie DP[SUP]3[/SUP], Crowe J[SUP]4[/SUP], Rossjohn J[SUP]5[/SUP], Xu J[SUP]6[/SUP], Doherty PC[SUP]7[/SUP], McCluskey J[SUP]1[/SUP], Kedzierska K[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+[/SUP]Vα7.2[SUP]+[/SUP] 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[SUP]+[/SUP]CD3[SUP]-[/SUP]) 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[SUP]+[/SUP] 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.
[h=4]KEYWORDS:[/h] H7N9; IL-18; MAIT cells; influenza virus; monocytes
PMID: 27543331 DOI: 10.1073/pnas.1610750113
[PubMed - as supplied by publisher] Free full text