Interferon-Associated Transcriptional Responses Are Preserved in Human Asthmatic Airway Epithelial Cells During Viral...

Viral infections are the main cause of asthma exacerbation, particularly in children. Impaired interferon induction by the airway epithelium has been linked to increased asthma exacerbation during viral infections. Several studies have suggested that epithelial cells in asthmatic mice induce low levels of type I and type III interferons, which leads to increased viral load. However, emerging evidence suggests that epithelial cells from asthmatic individuals induce delayed interferon responses. This study aimed to assess the ability of asthmatic and healthy epithelial cells to mount interferon-associated responses after exposure to viral stimuli. Variations in gene expression associated with interferon response were analyzed using datasets obtained from the Gene Expression Omnibus (GEO) database. Airway epithelial cells derived from healthy and asthmatic individuals were infected with RNA virus and then subjected to microarray or RNA sequencing. Lung tissues obtained from the animal models (mice and rats) were analyzed using RNA sequencing. Further data analysis was performed using integrated differential expression and pathway analysis (iDEP). Viral infection of airway epithelial cells derived from healthy and asthmatic subjects induces strong expression of interferon- and interferon-related genes. Interferon-stimulated genes (ISGs) were robustly induced in both asthmatic and healthy human epithelial cells after viral infection. However, the induction of virus-induced interferon-related responses was significantly lower in the lung tissues of animals with pre-allergic inflammation. Although previous studies have reported that the antiviral-interferon response is impaired or diminished in asthmatic individuals, our findings suggest that interferon-associated transcriptional responses are preserved in the airway epithelial cells of asthmatics during viral infection. This suggests that asthmatic epithelial cells induce an antiviral immune response, characterized by the induction of interferon-associated genes necessary for viral removal. Future studies should investigate the mechanisms underlying virus-induced asthma exacerbation.