Interleukin-18 improves the early defence system against influenza virus infection by augmenting natural killer cell-mediated cytotoxicity
Interleukin-18 improves the early defence system against influenza virus infection by augmenting natural killer cell-mediated cytotoxicity
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DOI：
10.1099/vir.0.19596-0
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发表时间：
2004-02-01
影响因子：
3.8
通讯作者：
Kimura, Y
中科院分区：
文献类型：
--
作者：
Liu, BX;Mori, I;Kimura, Y
本文研究了白细胞介素（IC）-18（IL-18）在流感病毒感染宿主防御系统发育中的作用。鼻内接种人流感A/PR/8/34（H1N1）病毒小鼠适应株的IL-18缺陷型（IL-18（-/-））C57 BL/6小鼠显示死亡率增加，在感染的前3天肺部发生致病性变化，包括明显的病毒生长伴大量炎性细胞浸润和一氧化氮产生增加。在病毒感染后的最初几天，IL-18（-/-）小鼠呼吸道中诱导的干扰素-γ（IFN-γ）水平显著较低，但相比之下，IL-12水平略高于野生型C57 BL/6小鼠中的相应水平。IL-18（-/-）小鼠肺中自然杀伤（NK）细胞介导的细胞毒性活化较差。两种品系的小鼠在流感病毒感染后同样诱导肺中的局部免疫应答，如特异性细胞毒性T淋巴细胞和抗体产生。这些结果表明，IL-18参与控制肺中的流感病毒复制，特别是在感染的早期阶段，通过激活先天免疫机制如IFN和NK细胞。
The role of interleukin (IC)-18 in the development of the host defence system against influenza virus infection was investigated. IL-18-deficient (IL-18(-/-)) C57BL/6 mice that were inoculated intranasally with the mouse-adapted strain of human influenza A/PR/8/34 (H1N1)virus showed an increased mortality with the occurrence of pathogenic changes in the lung for the first 3 days of infection, which included pronounced virus growth with massive infiltration of inflammatory cells and elevated nitric oxide production. The interferon-gamma (IFN-gamma) level induced in the respiratory tract of IL-18(-/-) mice in the first few days after virus infection was significantly lower but, in contrast, the IL-12 level was slightly higher than the corresponding levels in wild-type C57BL/6 mice. Natural killer (NK) cell-mediated cytotoxicity in the lung of IL-18(-/-) mice was poorly activated. Local immune responses in the lung such as specific cytotoxic T lymphocyte and antibody production were induced upon influenza virus infection equally well in both strains of mice. These results indicate that IL-18 is involved in controlling influenza virus replication in the lung, especially at an early stage of infection, through activation of the innate immune mechanisms such as IFN and NK cells.