Type I interferon and interferon-stimulated gene expression in oral epithelial cells
Type I interferon and interferon-stimulated gene expression in oral epithelial cells
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DOI：
10.1111/omi.12270
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发表时间：
2019-10-21
影响因子：
3.7
通讯作者：
Diamond, G.
中科院分区：
文献类型：
--
作者：
Brice, D. C.;Figgins, E.;Diamond, G.
口腔上皮细胞(OEC)是宿主与通过口腔途径感染机体的病毒相互作用的第一个部位；然而，其固有的抗病毒防御机制尚未明确。以往的研究已经确定OEC表达病原体、损伤或危险相关的分子模式(PAMP或DAMP)，但其关键的抗病毒天然免疫介质，包括I型干扰素(I型干扰素)和干扰素刺激基因(ISGs)的表达尚未被广泛研究。我们使用口腔角质形成细胞系OKF6/TERT1，在病毒模拟物Poly(I：C)和未甲基化的CpG DNA存在和不存在的情况下，确定I型干扰素和ISGs的表达。我们鉴定了新的I型干扰素基因IFNe和IFNK的基础表达，而IFNB1是由病毒模拟物通过IRF3的核易位诱导的。在OEC中，大量ISGs在基础水平上表达，在病毒感染的早期阶段，高表达与抗病毒活性明显相关。Poly(I：C)刺激嗅鞘细胞可选择性诱导ISGs，包括MX1、BST2、PML、RSAD2、ISG15和ZC3HAV1。综上所述，我们的结果表明，嗅鞘细胞表现出强大的先天抗病毒免疫防御特性，这是为应对各种口头传播的致病病毒而准备的。
Oral epithelial cells (OEC) represent the first site of host interaction with viruses that infect the body through the oral route; however, their innate antiviral defense mechanisms yet to be defined. Previous studies have determined that OEC express pathogen-, damage-, or danger-associated molecular patterns (PAMPs or DAMPs), but their expression of key antiviral innate immune mediators, including type I interferons (type I IFN) and interferon-stimulated genes (ISGs) has not been studied extensively. We used the oral keratinocyte cell line, OKF6/TERT1, in the presence and absence of the viral mimics poly(I:C) and unmethylated CpG DNA, to define the expression of type I IFN and ISGs. We identified the basal expression of novel type I IFN genes IFNE and IFNK, while IFNB1 was induced by viral mimics, through the nuclear translocation of IRF3. Numerous ISGs were expressed at basal levels in OEC, with an apparent correlation between high expression and antiviral activity at the earlier stages of viral infection. Stimulation of OECs with poly(I:C) led to selective induction of ISGs, including MX1, BST2, PML, RSAD2, ISG15, and ZC3HAV1. Together, our results demonstrate that OECs exhibit a robust innate antiviral immune defense profile, which is primed to address a wide variety of pathogenic viruses that are transmitted orally.