Ex vivo modeling of nasal epithelial airway inflammation in respiratory viral infections

Background – Early inflammatory responses at the nasal airway epithelium, the primary portal of entry for respiratory viruses, remain unclear. Primary airway cell culture models have yielded contradictory results due to heterogeneity among donors and variable processing of airway cells. Methods – Using a novel polarized ex vivo culture system of primary, immortalized human nasal epithelial cells (hNECs) in air-liquid interface (ALI) culture, we compared inflammatory responses following infection with human rhinovirus (HRV16) or influenza virus. Results – Over 24 and 48 h, both HRV16 and H1N1-PR8 consistently and similarly increased levels of apical and basal TNF-α, and VEGF. HRV16 differentially increased secretion of IL-1β, IL-6, IL-8, and IL-10 levels in apical or basal surfaces compared to H1N1-PR8. Both HRV16 and H1N1-PR8 induced significant upregulation of VEGF, a mediator of angiogenesis. Both HRV16 and H1N1-PR8 induced much greater upregulation of apical rather than basal IL-6 secretion. Conclusion – Our data provide mechanistic insight into the pro-inflammatory effects of respiratory viruses on nasal secretions and show that both HRV and influenza A induce a marked increase in the secretion of IL-1β, IL-6, and VEGF from human nasal airway epithelium, offering a possible mechanism for influenza-mediated nasal congestion. This model enables controlled investigation of early nasal epithelial host–virus interactions in physiologically relevant polarization, to explore host-virus nasal airway interactions.