Journal Article

Genome-Wide Gene Expression Analysis Reveals Unique Genes Signatures of Epithelial Reorganization in Primary Airway Epithelium Induced by Type-I, -II and -III Interferons

Erb, Anna, Schmidt-Weber, Carsten B., Chaker, Adam M., Jakwerth, Constanze A., Zissler, Ulrich M., Oelsner, Madlen

2022

Overview

Biosensors such as toll-like receptors (TLR) induce the expression of interferons (IFNs) after viral infection that are critical to the first step in cell-intrinsic host defense mechanisms. Their differential influence on epithelial integrity genes, however, remains elusive. A genome-wide gene expression biosensor chip for gene expression sensing was used to examine the effects of type-I, -II, and -III IFN stimulation on the epithelial expression profiles of primary organotypic 3D air-liquid interface airway cultures. All types of IFNs induced similar interferon-stimulated genes (ISGs): OAS1, OAS2, and IFIT2. However, they differentially induced transcription factors, epithelial modulators, and pro-inflammatory genes. Type-I IFN-induced genes were associated with cell–cell adhesion and tight junctions, while type-III IFNs promoted genes important for transepithelial transport. In contrast, type-II IFN stimulated proliferation-triggering genes associated and enhanced pro-inflammatory mediator secretion. In conclusion, with our microarray system, we provide evidence that the three IFN types exceed their antiviral ISG-response by inducing distinct remodeling processes, thereby likely strengthening the epithelial airway barrier by enhancing cross-cell-integrity (I), transepithelial transport (III) and finally reconstruction through proliferation (II).

• Publisher: MDPI AG,MDPI
• Subject: Airway (Medicine) / airway epithelial / Antigens / Antiviral Agents - pharmacology / Antiviral drugs / Biosensors / Cell adhesion / Cytokines / Defense mechanisms / Dendritic cells / Development and progression / DNA microarrays / epithelial integrity / Epithelium / Epithelium - metabolism / Gene Expression / gene expression analysis / Genes / Genetic aspects / Genomes / Health aspects / II and -III Interferons / Immune response / Inflammation / Integrity / Interferon / Interferon Type I - genetics / Interferon Type I - metabolism / Interferon Type I - pharmacology / microarray / Modulators / Pathogens / Physiological aspects / Proteins / Respiratory tract / Severe acute respiratory syndrome coronavirus 2 / Tight junctions / Toll-like receptors / Transcription factors / type-I / Viral infections / Virus diseases