Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC 1401, 33000 Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux U1045, Plateforme Transcriptome Neurocentre Magendie U1215, Functionnal Genomics Center (CGFB) Proteomics Facility, CIC 1401, PTIB - Hôpital Xavier Arnozan, Avenue du Haut Lévêque, 33600 PESSAC, 33000 Bordeaux, France.
Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC 1401, 33000 Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux U1045, Plateforme Transcriptome Neurocentre Magendie U1215, Functionnal Genomics Center (CGFB) Proteomics Facility, CIC 1401, PTIB - Hôpital Xavier Arnozan, Avenue du Haut Lévêque, 33600 PESSAC, 33000 Bordeaux, France; CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pharmacologie, CIC 1401, Service de chirurgie thoracique, 33604 Pessac, France.
Cell Rep. 2022 Mar 29;38(13):110571. doi: 10.1016/j.celrep.2022.110571.
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.
鼻病毒（RV）感染支气管上皮与绝大多数严重哮喘恶化有关。有趣的是，哮喘患者支气管上皮对 RV 感染的易感性增加。支气管平滑肌（BSM）重塑是严重哮喘病理生理学的一个重要特征，使用支气管热成形术减少其重塑与哮喘恶化率的显著降低有关。我们假设哮喘的 BSM 可能在支气管上皮的 RV 感染中发挥作用。我们使用支气管上皮和 BSM 细胞之间的原始共培养模型，显示哮喘的 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 细胞增加 CCL20 的产生有关。此外，我们证明了上皮蛋白激酶 RNA 激活（PKR）抗病毒途径的活性被下调。最后，我们发现哮喘的 BSM 细胞对支气管上皮对 RV 感染的易感性具有直接的自上而下的影响。
