Modulation of airway epithelial antiviral immunity by fungal exposure.

Modulation of airway epithelial antiviral immunity by fungal exposure.
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通过真菌暴露调节气道上皮抗病毒免疫。

DOI:
10.1165/rcmb.2013-0357oc
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发表时间:
2014
影响因子:
6.4
通讯作者:
Chen,Yin
Chen,Yin
中科院分区:
医学1区
文献类型:
--
作者:
Zhu,Lingxiang;Lee,Boram;Zhao,Fangkun;Zhou,Xu;Chin,Vanessa;Ling,SerenaC;Chen,Yin

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哮喘气道中经常发现多种病原体,如细菌、真菌和病毒,它们与哮喘的发病和加重有关。在这些病原体中,普遍存在的真菌交替孢霉(Alternaria alternata,Alt)和人类鼻病毒已被广泛研究。然而,它们之间的相互作用尚未被研究。在本研究中,我们使用活病毒和合成病毒模拟物双链RNA (dsRNA)测试了Alt暴露对病毒诱导的气道上皮免疫的影响。Alt治疗可显著提高病毒感染或dsRNA治疗诱导的促炎细胞因子(如IL-6和IL-8)的产生。与这种协同作用相反,Alt显著抑制I型和III型IFN的产生,这种损害导致病毒复制升高。机制研究表明,NF-κB和丝裂原活化蛋白激酶途径在抑制IFN产生的TBK1-IRF3途径的协同作用和衰减中发挥了积极作用。这些相反的效果是由不同的真菌成分引起的。蛋白酶依赖性和非依赖性机制似乎参与其中。因此,Alt暴露改变了气道上皮对病毒感染的免疫,转向更炎症但更少抗病毒反应。
Multiple pathogens, such as bacteria, fungi, and viruses, have been frequently found in asthmatic airways and are associated with the pathogenesis and exacerbation of asthma. Among these pathogens,Alternaria alternata(Alt), a universally present fungus, and human rhinovirus have been extensively studied. However, their interactions have not been investigated. In the present study, we tested the effect of Alt exposure on virus-induced airway epithelial immunity using live virus and a synthetic viral mimicker, double-stranded RNA (dsRNA). Alt treatment was found to significantly enhance the production of proinflammatory cytokines (e.g., IL-6 and IL-8) induced by virus infection or dsRNA treatment. In contrast to this synergistic effect, Alt significantly repressed type I and type III IFN production, and this impairment led to elevated viral replication. Mechanistic studies suggested the positive role of NF-κB and mitogen-activated protein kinase pathways in the synergism and the attenuation of the TBK1-IRF3 pathway in the inhibition of IFN production. These opposite effects are caused by separate fungal components. Protease-dependent and -independent mechanisms appear to be involved. Thus, Alt exposure alters the airway epithelial immunity to viral infection by shifting toward more inflammatory but less antiviral responses.
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