Network Analysis Reveals Age- and Virus-Specific Circuits in Nasal Epithelial Cells of Extremely Premature Infants

Background and objectivesViral 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.MethodsUsing 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.ResultsOur 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.ConclusionThis 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. Extremely premature infants have a higher susceptibility to respiratory virus infections. NEC are critical in defending against respiratory infections. Age-dependent differences in innate NEC responses to influenza A and RSV were identified, revealing distinct receptor repertoires and antiviral network-circuits in neonatal versus adult cells. This highlights the significance of NEC immunity in age-related responses to viral infections. Abbreviations: ALI, air-liquid interface; CXCL8, chemokine C-X-C motif ligand 8; CX3CR1, CX3C motif chemokine receptor; IFN, interferon; IL, interleukin; NEC, nasal epithelial cells, RSV, respiratory syncytial virus; PRR, pattern recognition receptor; RNA-seq, RNA sequencing; TLR, Toll-like receptorimage