Asthmatic airway epithelial cells subjected to apical mechanical stress exhibit suppressed interferon release following viral infection

Abstract

Rationale: Bronchoconstriction (BC) is a hallmark of asthma and generates airway mechanical stress. During asthma exacerbations, BC occurs simultaneously with viral infection; the influence of BC on antiviral responses has not been investigated. We hypothesised that mechanical stresses generated during BC suppress epithelial innate immune responses following rhinovirus (RV) infection. Methods: Airway epithelial cells were obtained from asthmatic donors. Cells were cultured and differentiated at the air-liquid interface then apically compressed either prior to (“exacerbation model”, n=6) or following (“poor control model”, n=12) RV infection. Compression was applied for 10 minutes every hour for 4 days at 30cm H20 pressure. Samples were collected at 0, 24, 48, 72 and 96h following infection and were analysed for viral RNA, virus release, IFN-β and IFN-λ protein. Results: Compression suppressed the release of IFN-β and IFN-λ protein following RV infection from 48h post-infection in both the exacerbation model (Figure 1) and poor control model. Compression did not alter viral replication. Conclusion: Compression mimicking BC supresses anti-viral innate immune responses from asthmatic airway epithelial cells when applied both prior to and following RV infection. This may explain clinical findings that poorly controlled asthmatics have impaired anti-viral responses.