Cell and Molecular Biology Program, University of Southern Mississippi, Hattiesburg, MS.
Cell and Molecular Biology Program, University of Southern Mississippi, Hattiesburg, MS
J Immunol. 2022 Jun 15;208(12):2761-2770. doi: 10.4049/jimmunol.2100679. Epub 2022 Jun 1.
The blastocyst is the preimplantation stage embryo that consists of two major components: the inner cell mass (ICM) and the trophectoderm (TE). The ICM gives rise to the fetus and some extraembryonic tissues whereas the TE contributes to development of the placenta. Previous studies have demonstrated that both human and mouse embryonic stem cells (ESCs) derived from the ICM are deficient in expressing type I IFNs in response to viral infection. In this study, we investigated the IFN response in mouse trophoblast stem cells (TSCs) and their in vitro differentiated trophoblasts (TSC-TBs). In this study, we report that, unlike ESCs, TSCs have a functional IFN system. They can express type I IFNs in response to viral stimuli and express IFN-stimulated genes in response to type I IFNs. TSC-TBs have a further developed IFN system and acquired the ability to express specialized type III IFN-λ. Furthermore, TSCs and TSC-TBs can provide ESCs with antiviral activity against Chikungunya, West Nile, and Zika virus infection, as demonstrated with a novel coculture model that simulates the temporal and spatial relationship between the ICM and the TE in a blastocyst. Taken together, our data demonstrate that mouse ESCs can respond to type I IFNs and gain IFN-based antiviral protection from TSCs and TSC-TBs via paracrine signaling mechanisms even though they themselves are unable to express type I IFNs.
囊胚是植入前胚胎，由两个主要部分组成：内细胞团（ICM）和滋养外胚层（TE）。ICM 产生胎儿和一些胚胎外组织，而 TE 则有助于胎盘的发育。先前的研究表明，源自 ICM 的人和小鼠胚胎干细胞（ESCs）在病毒感染时都缺乏表达 I 型 IFNs 的能力。在这项研究中，我们研究了小鼠滋养层干细胞（TSCs）及其体外分化的滋养层细胞（TSC-TBs）中的 IFN 反应。在这项研究中，我们报告称，与 ESCs 不同，TSCs 具有功能性 IFN 系统。它们可以对病毒刺激物表达 I 型 IFNs，并对 I 型 IFNs 表达 IFN 刺激基因。TSC-TBs 具有进一步发育的 IFN 系统，并获得了表达特殊的 III 型 IFN-λ 的能力。此外，TSCs 和 TSC-TBs 可以为 ESCs 提供针对 Chikungunya、西尼罗河和寨卡病毒感染的抗病毒活性，这是通过一种新的共培养模型证明的，该模型模拟了囊胚中 ICM 和 TE 之间的时空关系。总之，我们的数据表明，尽管小鼠 ESCs 本身无法表达 I 型 IFNs，但它们可以通过旁分泌信号机制对 I 型 IFNs 做出反应，并从 TSCs 和 TSC-TBs 获得 IFN 为基础的抗病毒保护。
