Work

Cytokine responses to respiratory syncytial virus infection in well-differentiated infant nasal epithelial cell cultures

Year: 2025

Type: article

Abstract: Differentiated airway epithelial cell cultures closely mimic the in vivo airways.We compared the structure and cytokine response of well-differentiated human nasal epithelial (HNE) cells obtained from healthy infants (iHNE) and adults (aHNE).Materials and Methods: Human bronchial epithelial (HBE) progenitor (n=4) and primary HNE cells (n=4 aHNE; n=10 iHNE) were cultured using a modification of the air-liquid interface (ALI) approach.For differentiated HBE and HNE cell cultures, representative transwells were fixed and then stained for ciliated and goblet cells.Low (400 pfu) and high (10 5 pfu) inoculums of recombinant green fluorescent protein-expressing respiratory syncytial virus (RSV) were added apically to the ALI cultures.The concentrations of cytokines were measured in airway cell cultures using a bead-based immunoassay.Results: The morphology of HBE, iHNE, and aHNE cell cultures were comparable, but RSV replication and spread were more prominent in HBE and iHNE compared to aHNE.Among the 13 cytokines measured, we detected significant concentrations of six cytokines: interleukin (IL)-6, IP-10, interferon (IFN)-λ1, IL-8, IFN-λ2/3, and IFN-ß.Concentrations of IL-6, IFN-λ1, IFN-λ2/3, IFN-ß, and IP-10 were significantly higher in HBE cell cultures than in aHNE and/or iHNE cell cultures.However, there were no differences in the cytokine concentrations measured in the aHNE and iHNE cell cultures.Conclusion: We established methods for obtaining, culturing, differentiating, and infecting iHNE cells, which were safe and highly reproducible.A more efficient RSV replication in infants upper airway cells than in cells from adults could be a factor contributing to the greater disease severity of RSV in infants.

Source: Clinical and Experimental Vaccine Research

DOI: 10.7774/cevr.2025.14.e30

Authors: Ki Wook Yun, Phylip Chen, Susan D. Reynolds, Asuncion Mejias, Mark E. Peeples, Octavio Ramilo