What question did this study set out to answer?

This research aims to explore how gestational and postnatal age influence airway epithelial responses to RSV in infants.

May 20, 2026Open Access

Gestational and postnatal age define airway epithelial maturation and RSV responses during the first year of life: results of an ex-vivo/in-vitro Airway Epithelial Cell Study

Key Points

This research aims to explore how gestational and postnatal age influence airway epithelial responses to RSV in infants.
Established ex-vivo/in-vitro cultures of well-differentiated pediatric nasal epithelial cells from preterm and term infants at birth and at 1 year old.
Analyzed RSV infection characteristics and innate immune responses in these cell cultures.
Conducted differential gene expression analysis to identify age- and gestation-related changes.
RSV infection led to similar growth kinetics and cytopathology in airway epithelial cells regardless of gestational age or postnatal age.
Increased secretion of IFN-λ1 and CCL5 was observed in 1-year-old compared to newborn-derived cells (p<0.05 and p<0.01, respectively).
Identified 156 differentially expressed genes linked to airway epithelial cell development from term to preterm infants and across the first year.

Abstract

Introduction Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection in infants globally. Newborns, especially those born prematurely, are at increased risk of severe RSV-related illness, yet the influence of age on early-life airway epithelium innate immune responses remains relatively understudied. Methods We established ex-vivo/in-vitro well-differentiated paediatric nasal epithelial cell (WD-PNEC) cultures derived from preterm and term infants at birth and again at 1-year old. Infection characteristics and innate immune responses were determined following in vitro RSV infection. Results RSV growth kinetics and cytopathology were similar irrespective of gestation or age. Secretion of interferon lambda-1 (IFN-λ1), CXCL10, CCL5 and CXCL8 was comparable between RSV-infected preterm-newborn and term-newborn WD-PNECs. Importantly, following RSV infection, secretion of RSV-induced IFN-λ1 (p<0.05) and CCL5 (p<0.01) and expression of the IFN-stimulated gene, IFN-alpha inducible protein 6 ( IFI6) (p<0.05) were significantly higher in 1 year- compared with newborn-derived WD-PNECs. Interestingly, secretion of the cell signalling cytokine pleiotrophin increased significantly with longer gestation (p<0.01) and older age (p<0.001). Differential gene expression analysis demonstrated 156 differentially expressed genes (DEGs) with age and revealed transcriptomic changes linked to gestation in newborns that persisted at 1 year. Conclusion These findings indicate two major conclusions. First, we report transcriptomic differences in airway epithelial cell (AEC) development between term and preterm infants across the first year of life. Second, we demonstrate that RSV infection responses of AECs become more robust with age in early life. Further investigation of identified DEGs and differentially expressed chemokines/cytokines is warranted to clarify their role in increased susceptibility of very young infants to severe RSV disease as well as the significance of these factors in the emergence of wheezing phenotypes and long-term respiratory outcomes.

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Groves et al. (Mon,) studied this question.

synapsesocial.com/papers/6a0d5098f03e14405aa9c8dc https://doi.org/https://doi.org/10.1136/thorax-2025-224127

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