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BackgroundBacterial respiratory tract infections and exacerbations of chronic lung diseases are commonly caused by nontypeable Haemophilus influenzae (NTHi). Cell-mediated cytotoxicity may be key to controlling infection, but the responses of NTHi-specific T cell populations are not well understood. Mucosal-associated invariant T (MAIT) cells are a recently-discovered, innate-like subset of T cells with cytotoxic function, whose role in lung immunity is unclear. ObjectiveThe aim of this study was to determine the mechanisms behind conventional T and MAIT cell cytotoxic responses to NTHi. MethodsHuman ex vivo lung explants were infected with a clinical strain of NTHi. Monocyte-derived macrophages were also infected with NTHi in vitro and co-cultured with autologous T cells. Cytotoxic responses of T cell subsets were measured by flow cytometry. ResultsWe found significant upregulation of the cytotoxic markers, CD107a and granzyme B, in lung CD4+, CD8+ and MAIT cell populations. We show that MAIT cell cytotoxic responses were upregulated by a combination of both time-dependent antigen presentation and through a novel mechanism by which IL-12 and IL-7 synergistically control granzyme B through upregulation of the IL-12 receptor. ConclusionsOverall our data provide evidence for a cytotoxic role of MAIT cells in the lung and highlight important differences in the control of adaptive and innate-like T cell responses. Understanding these mechanisms may lead to new therapeutic opportunities to modulate the anti-bacterial response and improve clinical outcome.