Human mucosal associated invariant T cells contribute to antiviral influenza immunity via IL 18 dependent activation
Significance Mucosal associated invariant T (MAIT) cells are innate like T lymphocytes with potent antibacterial reactivity. In this study, we investigated whether MAIT cells also contribute to immunity against influenza A viruses. Compared with those who succumbed, hospitalized patients who recovered from severe avian H7N9 influenza infection had higher numbers of MAIT cells. Subsequent in vitro analysis established that MAIT cells from healthy donors are indirectly activated by influenza infection via an IL 18 dependent (but not IL 12 dependent) mechanism requiring the involvement of CD14+ monocytes. Our findings highlight the potential for MAIT cells to promote protective immunity in human influenza. 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+Va7.2+ 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 IFNg 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.
Proceedings of the National Academy of Sciences