Rhinovirus triggers increased inflammasome activation in human bronchial epithelium in asthma

Abstract

There is strong evidence of the role of house dust mite (HDM) and human rhinovirus (HRV-16) in exacerbations of asthma. Airway epithelium provides protection against inhaled factors through various pattern recognition receptors (PRRs). Some of PRRs were shown to assemble into inflammasomes, leading to secretion of mature IL-1β and IL-18. There are limited data on activation of inflammasome in differentiated human bronchial epithelium in asthma and its exacerbations. First, we performed next generation sequencing of bronchial epithelial cells from asthmatic and healthy donors. There were several inflammasome-related pathways enriched in asthma patients. Next, we performed air-liquid interface cultures of bronchial epithelium with HDM stimulation and HRV-16 infection, analyzed by RT-PCR, WB, ELISA and confocal microscopy. We found significantly increased inflammasome activation in asthmatics, confirmed by the presence of ASC specks, activated caspase-1 and elevated expression of secreted mature IL-1β upon HRV-16 alone and combined HDM and HRV-16 stimulation, blocked by caspase-1 inhibitor. Moreover, ASC expression in the bronchial wall biopsies of asthmatic patients was enhanced in the upper layers of epithelium and was accompanied with the increased IL-1β levels in BAL. Moreover, we found that in acute and chronic high dose-HDM-induced model of airway inflammation in mice ASC, caspase-1 and IL-1β mRNA is significantly increased in the lungs. Our findings highlight the role of bronchial epithelium as essential inflammatory reservoir upon HRV infection combined with HDM exposure. Induction of rapid IL-1β secretion might have an impact on asthma exacerbations.