Type I interferon limits influenza virus-induced acute lung injury by regulation of excessive inflammation in mice

Yojiro Arimori, Risa Nakamura, Hisakata Yamada, Kensuke Shibata, Naoyoshi Maeda, Tetsuo Kase, Yasunobu Yoshikai

Research output: Contribution to journalArticle

52 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)230-237
Number of pages8
JournalAntiviral Research
Volume99
Issue number3
DOIs
Publication statusPublished - Sep 1 2013

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Interferon Type I
Acute Lung Injury
Influenza A virus
Orthomyxoviridae
Knockout Mice
Interleukin-10
Inflammation
Virus Diseases
Infection
Viral Load
Antiviral Agents
Interferon Receptors
Cytokines
Lung
Mortality
Anti-Inflammatory Agents
Viruses
Morbidity

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

Cite this

Type I interferon limits influenza virus-induced acute lung injury by regulation of excessive inflammation in mice. / Arimori, Yojiro; Nakamura, Risa; Yamada, Hisakata; Shibata, Kensuke; Maeda, Naoyoshi; Kase, Tetsuo; Yoshikai, Yasunobu.

In: Antiviral Research, Vol. 99, No. 3, 01.09.2013, p. 230-237.

Research output: Contribution to journalArticle

Arimori, Yojiro ; Nakamura, Risa ; Yamada, Hisakata ; Shibata, Kensuke ; Maeda, Naoyoshi ; Kase, Tetsuo ; Yoshikai, Yasunobu. / Type I interferon limits influenza virus-induced acute lung injury by regulation of excessive inflammation in mice. In: Antiviral Research. 2013 ; Vol. 99, No. 3. pp. 230-237.
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