哮喘支气管平滑肌增加鼻病毒在支气管上皮内的复制

2022/04/19

   摘要
   支气管上皮鼻病毒(RV)感染与绝大多数严重哮喘恶化有关。有趣的是,哮喘患者的支气管上皮对RV感染的易感性增加。支气管平滑肌(BSM)重塑是重症哮喘病理生理学的一个重要特征,使用支气管热成形术降低其重塑与显著降低恶化率相关。我们假设哮喘BSM可能在支气管上皮RV感染中发挥作用。使用支气管上皮和BSM细胞之间的原始共培养模型,我们发现哮喘BSM细胞在RV感染后增加了支气管上皮中的RV复制。这些发现与哮喘BSM细胞产生CCL20的增加有关。此外,我们还证明了上皮蛋白激酶RNA激活(PKR)抗病毒途径活性的最初下调。最后,我们确定了哮喘BSM细胞对支气管上皮对RV感染易感性的直接自底向上效应。

 
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Cell Rep. 2022 Mar 29;38(13):110571. doi: 10.1016/j.celrep.2022.110571.)


 
Asthmatic bronchial smooth muscle increases rhinovirus replication within the bronchial epithelium
 
Pauline Esteves, Benoit Allard, Alexis Celle, Isabelle Dupin, Elise Maurat, Olga Ousova, Matthieu Thumerel, Jean-William Dupuy, Thierry Leste-Lasserre, Roger Marthan, Pierre-Olivier Girodet, Thomas Trian, Patrick Berger
 
Abstract
Rhinovirus (RV) infection of the bronchial epithelium is implicated in the vast majority of severe asthma exacerbations. Interestingly, the susceptibility of bronchial epithelium to RV infection is increased in persons with asthma. Bronchial smooth muscle (BSM) remodeling is an important feature of severe asthma pathophysiology, and its reduction using bronchial thermoplasty has been associated with a significant decrease in the exacerbation rate. We hypothesized that asthmatic BSM can play a role in RV infection of the bronchial epithelium. Using an original co-culture model between bronchial epithelium and BSM cells, we show that asthmatic BSM cells increase RV replication in bronchial epithelium following RV infection. These findings are related to the increased production of CCL20 by asthmatic BSM cells. Moreover, we demonstrate an original downregulation of the activity of the epithelial protein kinase RNA-activated (PKR) antiviral pathway. Finally, we identify a direct bottom-up effect of asthmatic BSM cells on bronchial epithelium susceptibility to RV infection.

 
 


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