Inflammatory epithelial cytokines after in vitro respiratory syncytial viral infection are associated with reduced lung function

Wenming Duan; Yuchen Cen; Cindy Lin; Hong Ouyang; Kai Du; Anushree Kumar; Borui Wang; Julie Avolio; Hartmut Grasemann; Theo J Moraes

doi:10.1183/23120541.00365-2021

Inflammatory epithelial cytokines after in vitro respiratory syncytial viral infection are associated with reduced lung function

ERJ Open Res. 2021 Sep 13;7(3):00365-2021. doi: 10.1183/23120541.00365-2021. eCollection 2021 Jul.

Authors

Wenming Duan¹, Yuchen Cen^{1

2}, Cindy Lin¹, Hong Ouyang¹, Kai Du³, Anushree Kumar¹, Borui Wang¹, Julie Avolio¹, Hartmut Grasemann^{1

4}, Theo J Moraes^{1

2

4}

Affiliations

¹ Program in Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada.
² Dept of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
³ Program in Molecular Medicine, Hospital for Sick Children, Toronto, ON, Canada.
⁴ Division of Respiratory Medicine, Dept of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada.

Abstract

Respiratory syncytial virus (RSV) infections in early life predispose children with cystic fibrosis (CF) to more severe lung function decline in later life. The mechanisms explaining the associations between RSV and progression of CF lung disease are not clear. In this study, a human bronchial epithelial cell line and primary human nasal epithelial cells (PNECs) from individuals with CF and healthy control donors were infected with RSV. Real-time PCR, plaque assay, cytokine detection, immunofluorescence and Western blot analyses were performed. RSV is replicated to a higher degree in CF epithelial cells as compared to control cells; however, no defects in innate immune pathways were identified in CF cells. Rather, primary p.Phe508del cystic fibrosis transmembrane conductance regulator PNECs produced more cytokines after RSV infection than control cells. Moreover, interleukin-8 and tumour necrosis factor-α production post RSV negatively correlated with lung function (% predicted forced expiratory volume in 1 s) in the individuals who donated the cells. These data suggest that CF epithelium has a dysfunctional response to RSV allowing for enhanced viral replication and an exaggerated inflammatory response that ultimately may predispose to greater airway inflammation and reduced lung function.