Supplementary Material for: Type I Interferon Plays Opposing Roles in Cytotoxicity and Interferon-γ Production by Natural Killer and CD8<sup>+</sup> T Cells after Influenza A Virus Infection in Mice

Type I interferons (IFNs) promote natural killer (NK) and CD8<sup>+</sup> 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 <i>(Ifnar1</i><sup><i>-/-</i></sup><i>)</i> mice exhibited impaired cytotoxic activity as well as an increased ability of NK and CD8<sup>+</sup> 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<sup>+</sup> T cells in <i>Ifnar1</i><sup>-/-</sup> mice improved the survival rate after A/FM/1/47 infection, indicating that NK cells are responsible for acute lung injury in <i>Ifnar1</i><sup>-/-</sup> 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<sup>+</sup> T cells via IL-10 production.