Type I interferons (IFNs) promote natural killer (NK) and CD8+ T-cell responses, which play a role not only in the resolution of infection but also in the induction of acute lung injury following influenza A virus infection. We show here that IFN-α receptor knock-out (Ifnar1-/-) mice exhibited impaired cytotoxic activity as well as an increased ability of NK and CD8+ T cells to produce IFN-γ after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain). A deficiency in IFNAR signaling significantly impaired IL-10 production in influenza virus-infected lungs and enhanced IFN-γ production by NK cells, which were suppressed by exogenous IL-10. Depletion of NK cells but not CD8+ T cells in Ifnar1-/- mice improved the survival rate after A/FM/1/47 infection, indicating that NK cells are responsible for acute lung injury in Ifnar1-/- mice following influenza A virus infection, although the depletion of IFN-γ did not improve the outcome. Thus, type I IFN signaling plays a role not only in the upregulation of cytotoxicity but also in the downregulation of some effector mechanisms including IFN-γ production by NK and CD8+ T cells via IL-10 production.

Keywords:
Natural killer cell, CD8+ T cell, Interferon-γ, Type I interferon, Influenza, Cytotoxicity
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2014
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