Type I interferon limits influenza virus-induced acute lung injury by regulation of excessive inflammation in mice
Type I interferon limits influenza virus-induced acute lung injury by regulation of excessive inflammation in mice
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DOI：
10.1016/j.antiviral.2013.05.007
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发表时间：
2013-09-01
影响因子：
7.6
通讯作者：
Yoshikai, Yasunobu
中科院分区：
文献类型：
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作者：
Arimori, Yojiro;Nakamura, Risa;Yoshikai, Yasunobu
抗病毒免疫应答是解决高致病性甲型流感病毒感染和急性肺损伤发病机制的一把双刃剑。在这里，我们表明，I型干扰素（IFN）是重要的保护急性甲型流感病毒感染，不仅通过其抗病毒活性，而且通过其抗炎活性。与野生型（WT）小鼠相比，IFN α受体（IFNAR）敲除（KO）小鼠在感染流感病毒A/FM/1/47（H1N1，一种小鼠适应株）后表现出更高的病毒载量增加的死亡率和发病率，尽管两组中的病毒最终都被消除。在感染过程中，IFNAR KO小鼠肺中促炎细胞因子的水平显著高于WT小鼠，而肺中IL-10的水平显著低于WT小鼠。在持续的病毒感染期间IL-10的恢复显著降低了促炎细胞因子的水平并改善了IFNAR KO小鼠的死亡率。这些结果表明，I型IFN不仅负责直接解决病毒载量，而且还负责通过IL-10产生抑制由甲型流感病毒引起的免疫病理学。(C)2013爱思唯尔有限公司版权所有。
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 alpha 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. (C) 2013 Elsevier B.V. All rights reserved.