Interferon response to RSV by bronchial epithelium from children with asthma is inversely correlated with pulmonary function

Publication date: Available online 26 October 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): M.C. Altman, S.R. Reeves, A.R. Parker, E. Whalen, K.M.S. Misura, K.A. Barrow, R.G. James, T.S. Hallstrand, S.F. Ziegler, J.S. Debley
BackgroundRespiratory viral infection in early childhood, including that from respiratory syncytial virus (RSV), has been previously associated with the development of asthma.ObjectiveWe aimed to determine whether ex vivo RSV infection of bronchial epithelial cells (BECs) from children with asthma would induce specific gene expression patterns, and whether such patterns associate with lung function among BEC donors.MethodsPrimary BECs from carefully characterized children with asthma (n=18) and matched healthy children without asthma (n=8) were differentiated at an air-liquid interface (ALI) for 21 days. ALI cultures were infected with RSV for 96 hours and RNA was subsequently isolated from BECs. In each case, we analyzed gene expression using RNA sequencing and assessed differences between conditions by linear modeling of the data. BEC donors completed spirometry to measure lung function.ResultsRSV infection of BECs from subjects with asthma led to a significant increase in expression of 6927 genes compared to uninfected BECs. There was a significantly increased expression of 195 genes in BECs from children with asthma and airway obstruction (FEV1/FVC<0.85 and FEV1<100% predicted) compared to children with asthma without obstruction, as well as compared to healthy children. These specific genes were found to be highly enriched for viral response genes induced in parallel with type I and III IFNs.ConclusionBECs from children with asthma and with obstructive physiology exhibit greater expression of type I and type III IFN and IFN-stimulated genes than cells from children with normal lung function, and expression of IFN-associated genes correlates with the degree of airway obstruction. These findings suggest that an exaggerated IFN response to viral infection by airway epithelial cells may be a mechanism leading to lung function decline in a subset of children with asthma.

Teaser

RSV-infected bronchial epithelial cells from children with asthma and obstructive physiology demonstrate greater expression of type I and III IFN-associated genes than cells from children without airway obstruction. Furthermore expression of IFN-associated genes inversely correlate with lung function.


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