Horvath Mian, Yang Ruoyu, Castaneda Diana Cadena, Callender Megan, Aiken Elizabeth S, Voigt Anita Y, Caldwell Ryan, Fachi José, Di Luccia Blanda, Scholar Zoe, Yu Peter, Salner Andrew, Colonna Marco, Palucka Karolina, Oh Julia
The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA.
UCONN Health (University of Connecticut), Farmington, CT, 06030, USA.
BMC Biol. 2025 Jan 29;23(1):28. doi: 10.1186/s12915-025-02129-7.
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.
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.
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.
微生物群调节呼吸道上皮的免疫调节功能。为了探究微生物群的生物多样性如何影响微生物与上皮细胞的相互作用，我们筛选了58种系统发育上不同的微生物，以研究它们对人原代支气管气液界面（ALI）细胞培养物的转录组学影响。
我们发现宿主固有免疫和上皮屏障反应在物种和菌株水平上存在明显差异。令人惊讶的是，我们发现宿主干扰素（一种抗病毒反应）是宿主中变化最大的过程之一。这种变异性不是由微生物系统发育多样性、生物负荷或微生物刺激其他固有免疫途径的能力驱动的。
微生物定植以不同方式刺激宿主基因表达，在系统发育上不同的微生物以及同一物种的不同菌株之间均观察到了这种变化。我们的研究为理解呼吸道微生物群的生物多样性如何影响上皮，尤其是抗病毒固有免疫提供了基础。
