期刊
JOURNAL OF INFECTIOUS DISEASES
卷 204, 期 12, 页码 1866-1878出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jir665
关键词
-
资金
- Food and Health Bureau of Hong Kong SAR [10091062]
- Research Grant Council of Hong Kong SAR [7620/06M]
Highly pathogenic avian influenza H5N1 viruses cause severe disease in humans, and dysregulation of cytokine responses is believed to contribute to the pathogenesis of human H5N1 disease. However, mechanisms leading to the increased induction of proinflammatory cytokines by H5N1 viruses are poorly understood. We show that the innate sensing receptor RIG-I is involved in interferon regulatory factor 3 (IRF3), NF-kappa B nuclear translocation, p38 activation, and the subsequent interferon (IFN) beta, IFN-lambda 1, and tumor necrosis factor alpha induction during H5N1 infection. Soluble mediators from H5N1-infected human macrophages upregulate RIG-I, MDA5, and TLR3 to much higher levels than those from seasonal H1N1 in uninfected human macrophages and alveolar epithelial cells via paracrine IFNAR1/JAK but not IFN-lambda receptor signaling. Compared with H1N1 virus-induced mediators, H5N1 mediators markedly enhance the cytokine response to PolyIC and to both seasonal and H5N1 virus infection in a RIG-I-dependent manner. Thus, sensitizing neighboring cells by upregulation of RIG-I contributes to the amplified cytokine cascades during H5N1 infection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据