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

Allergy. 2024 Nov;79(11):3062-3081. doi: 10.1111/all.16196. Epub 2024 Jun 19.

Abstract

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.

Keywords: antiviral immunity; nasal epithelial cells; premature infants; respiratory infections; systems biology.

MeSH terms

  • Adult
  • Age Factors
  • Epithelial Cells* / immunology
  • Epithelial Cells* / virology
  • Humans
  • Immunity, Innate*
  • Infant, Extremely Premature* / immunology
  • Infant, Newborn
  • Influenza A virus / immunology
  • Nasal Mucosa* / cytology
  • Nasal Mucosa* / immunology
  • Nasal Mucosa* / virology
  • Respiratory Syncytial Virus Infections / immunology