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Updated: May 30, 2025

Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions
Published on: September 22, 2023
Species- and strain-specific microbial modulation of interferon, innate immunity, and epithelial barrier in 2D
Mian Horvath1,2, Ruoyu Yang1,2,3, Diana Cadena Castaneda1
1The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA.
Background:
The microbiome regulates the respiratory epithelium's immunomodulatory functions. To explore how the microbiome's biodiversity affects microbe-epithelial interactions, we screened 58 phylogenetically diverse microbes for their transcriptomic effect on human primary bronchial air-liquid interface (ALI) cell cultures.
Results:
We found distinct species- and strain-level differences in host innate immunity and epithelial barrier response. Strikingly, we found that host interferon, an antiviral response, was one of the most variable host processes. This variability was not driven by microbial phylogenetic diversity, bioburden, nor by the microbe's ability to stimulate other innate immunity pathways.
Conclusions:
Microbial colonization differentially stimulates host gene expression with variations observed across phylogenetically diverse microbes and across different strains of the same species. Our study provides a foundation for understanding how the respiratory microbiome's biodiversity affects epithelial, and particularly antiviral, innate immunity.

