Berman Reena, Jiang Di, Wu Qun, Stevenson Connor R, Schaefer Niccolette R, Chu Hong Wei
Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, United States of America.
PLoS One. 2016 Oct 4;11(10):e0163927. doi: 10.1371/journal.pone.0163927. eCollection 2016.
MUC18 is upregulated in the lungs of asthma and COPD patients. It has been shown to have pro-inflammatory functions in cultured human airway epithelial cells during viral infections and in mice during lung bacterial infections. However, the in vivo role of MUC18 in the context of viral infections remains poorly understood. The goal of this study is to define the in vivo function of MUC18 during respiratory rhinovirus infection.
Muc18 wild-type (WT) and knockout (KO) mice were infected with human rhinovirus 1B (HRV-1B) and sacrificed after 1 day to determine the inflammatory and antiviral responses. To examine the direct effects of Muc18 on viral infection, tracheal epithelial cells isolated from WT and KO mice were grown under air-liquid interface and infected with HRV-1B. Finally, siRNA mediated knockdown of MUC18 was performed in human airway epithelial cells (AECs) to define the impact of MUC18 on human airway response to HRV-1B.
Both viral load and neutrophilic inflammation were significantly decreased in Muc18 KO mice compared to WT mice. In the in vitro setting, viral load was significantly lower and antiviral gene expression was higher in airway epithelial cells of Muc18 KO mice than the WT mice. Furthermore, in MUC18 knockdown human AECs, viral load was decreased and antiviral gene expression was increased compared to controls.
Our study is the first to demonstrate MUC18's pro-inflammatory and pro-viral function in an in vivo mouse model of rhinovirus infection.
MUC18在哮喘和慢性阻塞性肺疾病（COPD）患者的肺部中表达上调。在病毒感染期间，MUC18在培养的人气道上皮细胞中以及在肺部细菌感染期间的小鼠中均表现出促炎功能。然而，MUC18在病毒感染背景下的体内作用仍知之甚少。本研究的目的是确定MUC18在呼吸道鼻病毒感染期间的体内功能。
用人类鼻病毒1B（HRV-1B）感染Muc18野生型（WT）和敲除（KO）小鼠，并在1天后处死以确定炎症和抗病毒反应。为了研究Muc18对病毒感染的直接影响，将从WT和KO小鼠分离的气管上皮细胞在气液界面下培养，并感染HRV-1B。最后，在人气道上皮细胞（AECs）中进行小干扰RNA（siRNA）介导的MUC18敲低，以确定MUC18对人呼吸道对HRV-1B反应的影响。
与WT小鼠相比，Muc18 KO小鼠的病毒载量和中性粒细胞炎症均显著降低。在体外实验中，Muc18 KO小鼠气道上皮细胞中的病毒载量显著低于WT小鼠，抗病毒基因表达则更高。此外，在MUC18敲低的人AECs中，与对照组相比，病毒载量降低，抗病毒基因表达增加。
我们的研究首次在鼻病毒感染的体内小鼠模型中证明了MUC18的促炎和促病毒功能。
