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 c... More
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.
