Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Public Oral Health, Program of Oral Health Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Oral Dis. 2022 Jan;28(1):150-163. doi: 10.1111/odi.13725. Epub 2020 Nov 30.
Double-strand (ds) DNA-enveloped viruses can cause oral infection. Our aim is to investigate whether oral mucosal cells participate in immune response against cytosolic dsDNA invasion.
We examined the response to transfected herpes simplex virus (HSV) dsDNA via intracellular receptors in oral keratinocytes (RT7) and fibroblasts (GT1), and the effect of TNF-α on those responses.
Transfected dsDNA increased CXCL10 expression via NF-κB activation in both cell types, while those responses were inhibited by knockdown of RIG-I, an RNA sensor. Although IFI16, a DNA sensor, was expressed in the nuclei of both types, its knockdown decreased transfected dsDNA-induced CXCL10 expression in GT1 but not RT7 cells. IFI16 in GT1 cells was translocated into cytoplasm from nuclei, which was attributed to immune response to cytosolic dsDNA. TNF-α enhanced transfected dsDNA-induced CXCL10, and knockdown of IFI16 decreased TNF-α and dsDNA-driven CXCL10 expression in both RT7 and GT1 cells. Finally, the combination of TNF-α and transfected dsDNA resulted in translocation of IFI16 from nuclei to cytoplasm in RT7 cells.
RIG-I and IFI16 in oral mucosal cells may play important roles in host immune response against DNA viral infection, while TNF-α contributes to development of an antiviral system via those intracellular receptors.
双链（ds）DNA 包膜病毒可引起口腔感染。本研究旨在探讨口腔黏膜细胞是否参与针对胞质 dsDNA 入侵的免疫反应。
我们通过口腔角质形成细胞（RT7）和纤维母细胞（GT1）中的细胞内受体检测了转染单纯疱疹病毒（HSV）dsDNA 的反应，以及 TNF-α 对这些反应的影响。
转染的 dsDNA 通过两种细胞类型中 NF-κB 的激活增加了 CXCL10 的表达，而 RIG-I（一种 RNA 传感器）的敲低抑制了这些反应。虽然两种细胞类型的核内均表达 DNA 传感器 IFI16，但敲低 IFI16 降低了 GT1 而非 RT7 细胞中转染 dsDNA 诱导的 CXCL10 表达。GT1 细胞中的 IFI16 从核内易位到细胞质，这归因于对胞质 dsDNA 的免疫反应。TNF-α 增强了转染 dsDNA 诱导的 CXCL10，IFI16 的敲低降低了 RT7 和 GT1 细胞中 TNF-α 和 dsDNA 驱动的 CXCL10 表达。最后，TNF-α 和转染 dsDNA 的组合导致 RT7 细胞中 IFI16 从核内易位到细胞质。
口腔黏膜细胞中的 RIG-I 和 IFI16 可能在宿主对 DNA 病毒感染的免疫反应中发挥重要作用，而 TNF-α 通过这些细胞内受体有助于抗病毒系统的发展。
