Type I interferon plays opposing roles in cytotoxicity and interferon-? production by natural killer and CD8 T cells after influenza A virus infection in mice.

ABSTRACT: 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-? receptor knock-out (Ifnar1(-/-)) mice exhibited impaired cytotoxic activity as well as an increased ability of NK and CD8(+) T cells to produce IFN-? 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-? 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-? 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-? production by NK and CD8(+) T cells via IL-10 production.

SUBMITTER: Arimori Y 

PROVIDER: S-EPMC6741478 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature