title: Type I interferon limits influenza virus-induced acute lung injury by regulation of excessive inflammation in mice.
abstract: Antiviral immune responses play as a double edged sword in resolution of infection and pathogenesis of acute lung injury caused by infection with highly pathogenic influenza A viruses. Here we show that type I interferons (IFNs) are important in protection against acute influenza A virus infection not only via their antiviral activity but also via their anti-inflammatory activity. IFN α receptor (IFNAR) knock-out (KO) mice exhibited increased mortality and morbidity with higher viral load after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) compared with wild-type (WT) mice, though the viruses were finally eliminated in both groups. The levels of proinflammatory cytokines in the lungs were significantly higher, while the level of IL-10 in the lungs was significantly lower in IFNAR KO mice than in WT mice during the course of infection. Restoration of IL-10 during an ongoing virus infection significantly reduced the levels of proinflammatory cytokines and improved mortality of IFNAR KO mice. These results suggest that type I IFNs are responsible not only for direct resolution of viral load but also for suppression of immunopathology caused by influenza A virus through IL-10 production.
authors.affiliation: Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, 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: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality / Q000821:virology; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality / Q000821:virology; D007370:Interferon Type I / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D016753:Interleukin-10; D053633:Receptor, Interferon alpha-beta
keywords: Acute lung injury; Influenza; Interleukin-10; Type I interferon