Schaller Research Group at CellNetworks, Department of Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany.
Research Group "Cellular Polarity and Viral Infection" (F140), German Cancer Research Center (DKFZ), Heidelberg, Germany.
J Interferon Cytokine Res. 2019 Oct;39(10):650-660. doi: 10.1089/jir.2019.0040. Epub 2019 Jun 13.
Intestinal epithelial cells (IECs) are the primary target of enteric viruses. Their infection by viruses leads to the upregulation of both type I and type III interferons (IFNs). These IFNs then act in an autocrine and paracrine manner to protect IECs from viral propagation. To date, whether both IFNs use similar signaling pathways and whether these 2 cytokines can act synergistically to protect against viral infection remain unclear. Using human IECs depleted of either the type I or type III IFN receptor, we found that both signal transduction pathways are interconnected and influence each other at the level of interferon-stimulated gene (ISG) expression and efficiency of antiviral protection. Precisely, in human IECs, the presence of a functional type III IFN receptor negatively regulates type I IFN signaling and activity, whereas the presence of type I IFN receptor positively reinforces type III IFN signaling and function. We propose that this complex crosstalk allows for a preferential type III IFN-mediated protection of human intestinal cells.
肠上皮细胞（IECs）是肠道病毒的主要靶标。病毒感染这些细胞会导致 I 型和 III 型干扰素（IFNs）的上调。这些 IFN 以自分泌和旁分泌的方式发挥作用，从而保护 IEC 免受病毒的增殖。迄今为止，尚不清楚这两种 IFN 是否使用相似的信号通路，以及这两种细胞因子是否可以协同作用以抵抗病毒感染。使用缺乏 I 型或 III 型 IFN 受体的人 IEC，我们发现两种信号转导途径相互关联，并在干扰素刺激基因（ISG）表达和抗病毒保护效率方面相互影响。确切地说，在人 IEC 中，功能性 III 型 IFN 受体的存在负调节 I 型 IFN 信号和活性，而 I 型 IFN 受体的存在则正向增强 III 型 IFN 信号和功能。我们提出，这种复杂的串扰允许人肠道细胞优先进行 III 型 IFN 介导的保护。
