Species- and Strain-specific Microbial Modulation of Interferon, Innate Immunity, and Epithelial Barrier in 2D Air-liquid Interface Respiratory Epithelial Cultures

Overview

Journal BMC Biol

Publisher Biomed Central

Date 2025 Jan 28

PMID 39875977

Authors

Mian Horvath

Ruoyu Yang

Diana Cadena Castaneda

Megan Callender

Elizabeth S Aiken

Anita Y Voigt

Ryan Caldwell

Jose Fachi

Blanda Di Luccia

Zoe Scholar

Peter Yu

Andrew Salner

Marco Colonna

Karolina Palucka

Julia Oh

Affiliations

Soon will be listed here.

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.

References

Koser C, Ellington M, Peacock S . Whole-genome sequencing to control antimicrobial resistance. Trends Genet. 2014; 30(9):401-7. PMC: 4156311. DOI: 10.1016/j.tig.2014.07.003. View

Seal R, Braschi B, Gray K, Jones T, Tweedie S, Haim-Vilmovsky L . Genenames.org: the HGNC resources in 2023. Nucleic Acids Res. 2022; 51(D1):D1003-D1009. PMC: 9825485. DOI: 10.1093/nar/gkac888. View

Edgar R . Search and clustering orders of magnitude faster than BLAST. Bioinformatics. 2010; 26(19):2460-1. DOI: 10.1093/bioinformatics/btq461. View

Parker D, Prince A . Staphylococcus aureus induces type I IFN signaling in dendritic cells via TLR9. J Immunol. 2012; 189(8):4040-6. PMC: 3466375. DOI: 10.4049/jimmunol.1201055. View

. UniProt: a hub for protein information. Nucleic Acids Res. 2014; 43(Database issue):D204-12. PMC: 4384041. DOI: 10.1093/nar/gku989. View

Schmieder R, Edwards R . Quality control and preprocessing of metagenomic datasets. Bioinformatics. 2011; 27(6):863-4. PMC: 3051327. DOI: 10.1093/bioinformatics/btr026. View

Seemann T . Prokka: rapid prokaryotic genome annotation. Bioinformatics. 2014; 30(14):2068-9. DOI: 10.1093/bioinformatics/btu153. View

Martin F, Gomez M, Wetzel D, Memmi G, OSeaghdha M, Soong G . Staphylococcus aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein A. J Clin Invest. 2009; 119(7):1931-9. PMC: 2701857. DOI: 10.1172/jci35879. View

Schoggins J, Rice C . Interferon-stimulated genes and their antiviral effector functions. Curr Opin Virol. 2012; 1(6):519-25. PMC: 3274382. DOI: 10.1016/j.coviro.2011.10.008. View

10.

Bassis C, Erb-Downward J, Dickson R, Freeman C, Schmidt T, Young V . Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. mBio. 2015; 6(2):e00037. PMC: 4358017. DOI: 10.1128/mBio.00037-15. View

11.

Cheng C, Hua Z . Lasso Peptides: Heterologous Production and Potential Medical Application. Front Bioeng Biotechnol. 2020; 8:571165. PMC: 7549694. DOI: 10.3389/fbioe.2020.571165. View

12.

Morey J, Kehl-Fie T . Bioinformatic Mapping of Opine-Like Zincophore Biosynthesis in Bacteria. mSystems. 2020; 5(4). PMC: 7438024. DOI: 10.1128/mSystems.00554-20. View

13.

. Structure, function and diversity of the healthy human microbiome. Nature. 2012; 486(7402):207-14. PMC: 3564958. DOI: 10.1038/nature11234. View

14.

Antunes K, Singanayagam A, Williams L, Faiez T, Farias A, Jackson M . Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection. J Allergy Clin Immunol. 2022; 151(2):447-457.e5. DOI: 10.1016/j.jaci.2022.09.026. View

15.

Leiva-Juarez M, Kolls J, Evans S . Lung epithelial cells: therapeutically inducible effectors of antimicrobial defense. Mucosal Immunol. 2017; 11(1):21-34. PMC: 5738267. DOI: 10.1038/mi.2017.71. View

16.

Liao Y, Smyth G, Shi W . featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2013; 30(7):923-30. DOI: 10.1093/bioinformatics/btt656. View

17.

Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z . clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation (Camb). 2021; 2(3):100141. PMC: 8454663. DOI: 10.1016/j.xinn.2021.100141. View

18.

Annunziato F, Romagnani C, Romagnani S . The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol. 2014; 135(3):626-35. DOI: 10.1016/j.jaci.2014.11.001. View

19.

Chaumeil P, Mussig A, Hugenholtz P, Parks D . GTDB-Tk v2: memory friendly classification with the genome taxonomy database. Bioinformatics. 2022; 38(23):5315-5316. PMC: 9710552. DOI: 10.1093/bioinformatics/btac672. View

20.

Yang X, Wang G, Xie J, Li H, Chen S, Liu W . The Intestinal Microbiome Primes Host Innate Immunity against Enteric Virus Systemic Infection through Type I Interferon. mBio. 2021; 12(3). PMC: 8262959. DOI: 10.1128/mBio.00366-21. View