Wilfred Gitau, University of Manitoba

Wilfred Gitau1,3, Fatemeh Sedaghat1,3, Julia A. Cerato1,3, Andrew J. Halayko2,3, Deanna M. Santer4, and Barbara N. Porto1,3 1Dept. of Medical Microbiology & Infectious Diseases, Rady Faculty of Health Sciences, University of Manitoba; 2Dept. Physiology & Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba; 3Biology of Breathing Theme, Children's Hospital Research Institute of Manitoba; 4Dept. of Immunology, Rady Faculty of Health Sciences, University of Manitoba.

Suppressing & Conquering

Introduction: Asthma is a chronic inflammatory disease of the airways characterized by recurrent wheezing. Allergens, such as house dust mite (HDM), disrupt airway epithelial barrier integrity and impair innate antiviral immunity, predisposing the airways to viral infections such as respiratory syncytial virus (RSV). RSV is a major trigger of asthma exacerbations and further impairs the production of interferons, critical for early viral clearance. Interferon lambda (IFN-λ), predominantly produced by epithelial cells, provides localized antiviral protection with minimal systemic inflammation, making it a promising therapeutic candidate. It remains unclear how HDM exposure worsens RSV infection and whether exogenous IFN-λ can mitigate HDM-enhanced RSV infection. Aim: To evaluate the protective effects of IFN-λ in HDM-enhanced RSV infection. Methodology: Human bronchial epithelial cells (HBECs) were treated with IFN-λ3 either before HDM or concurrently with HDM, followed by infection with RSV-GFP after 24h. Viral infection was assessed by mean fluorescence intensity and infection rate was calculated, while epithelial responses were evaluated through interferon-stimulated genes expression. For in vivo experiments, BALB/c mice were treated with IFN-λ3 24h prior to HDM exposure for 2 weeks. Bronchoalveolar lavage was collected to assess inflammatory cytokines and leukocytes, while lung tissue was harvested to evaluate inflammation and mucus secretion. Results: Exposure to HDM enhanced RSV infection in HBECs. Pretreatment with IFN-λ3 for 6h or concurrent treatment during HDM exposure significantly reduced HDM-enhanced RSV infection. Treating HDM-exposed mice with IFN-λ3 significantly decreased lung inflammation. Conclusion: Exogenous IFN-λ3 reduces HDM-enhanced RSV infection in HBECs and protects mice from HDM-induced airway inflammation.