Document Type

Article

Publication Date

1-29-2025

Publication Title

BMC biology [electronic resource]

Keywords

JGM, SS1, Immunity, Innate, Humans, Interferons, Microbiota, Respiratory Mucosa, Epithelial Cells, Species Specificity, Cells, Cultured

JAX Source

BMC Biol. 2025;23(1):28.

Volume

23

Issue

1

First Page

28

Last Page

28

ISSN

1741-7007

PMID

39875977

DOI

https://doi.org/10.1186/s12915-025-02129-7

Abstract

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.

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