Asthmatic bronchial smooth muscle increases rhinovirus replication within the bronchial epithelium
Pauline Estèves, Benoît Allard, Alexis Celle, Isabelle Dupin, Élise Maurat, Olga Ousova, Matthieu Thumerel, Jean‐William Dupuy, Thierry Lesté-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.