Network analysis reveals age‐ and virus‐specific circuits in nasal epithelial cells of extremely premature infants

Background and objectives Viral respiratory infections significantly affect young children, particularly extremely premature infants, resulting in high hospitalization rates and increased health‐care burdens. Nasal epithelial cells, the primary defense against respiratory infections, are vital for understanding nasal immune responses and serve as a promising target for uncovering underlying molecular and cellular mechanisms. Methods Using a trans‐well pseudostratified nasal epithelial cell system, we examined age‐dependent developmental differences and antiviral responses to influenza A and respiratory syncytial virus through systems biology approaches. Results Our studies revealed differences in innate‐receptor repertoires, distinct developmental pathways, and differentially connected antiviral network circuits between neonatal and adult nasal epithelial cells. Consensus network analysis identified unique and shared cellular‐viral networks, emphasizing highly relevant virus‐specific pathways, independent of viral replication kinetics. Conclusion This research highlights the importance of nasal epithelial cells in innate antiviral immune responses and offers crucial insights that allow for a deeper understanding of age‐related differences in nasal epithelial cell immunity following respiratory virus infections.