Center of Allergy & Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, German Research Center for Environmental Health, Member of the German Center for Lung Research (DZL), CPC-M, Member of the Helmholtz I&I Initiative, 85746 Munich, Germany.
Department of Otorhinolaryngology and Head and Neck Surgery, Medical School, Technical University of Munich, 81675 Munich, Germany.
Biosensors (Basel). 2022 Oct 26;12(11):929. doi: 10.3390/bios12110929.
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).
生物传感器，如 Toll 样受体 (TLR)，在病毒感染后诱导干扰素 (IFN) 的表达，这对于细胞内在宿主防御机制的第一步至关重要。然而，它们对上皮完整性基因的不同影响仍不清楚。使用全基因组基因表达生物传感器芯片来检测 I 型、II 型和 III 型 IFN 刺激对原代器官型 3D 气液界面气道培养物的上皮表达谱的影响。所有类型的 IFN 都诱导相似的干扰素刺激基因 (ISG)：OAS1、OAS2 和 IFIT2。然而，它们以不同的方式诱导转录因子、上皮调节剂和促炎基因。I 型 IFN 诱导的基因与细胞间粘附和紧密连接有关，而 III 型 IFNs 促进了对跨上皮转运很重要的基因。相比之下，II 型 IFN 刺激与增殖相关的基因，并增强了促炎介质的分泌。总之，我们的微阵列系统提供了证据，证明三种 IFN 类型通过诱导不同的重塑过程，超过了它们的抗病毒 ISG 反应，从而通过增强细胞间完整性 (I)、跨上皮转运 (III)，最终通过增殖进行重建 (II)，可能增强上皮气道屏障。
