title: Type I interferon plays opposing roles in cytotoxicity and interferon-γ 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-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.
authors.affiliation: Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Arimori
authors.forename: Risa
authors.initials: R
authors.lastname: Nakamura
authors.forename: Hisakata
authors.initials: H
authors.lastname: Yamada
authors.forename: Kensuke
authors.initials: K
authors.lastname: Shibata
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Maeda
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kase
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology* / Q000821:virology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D009980:Influenza A virus / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology* / Q000821:virology; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D016898:Interferon-alpha; D016753:Interleukin-10; D053633:Receptor, Interferon alpha-beta; D007371:Interferon-gamma