Tsukada Tsuyoshi, Shimada Hiroki, Sakata-Haga Hiromi, Shoji Hiroki, Iizuka Hideaki, Hatta Toshihisa
Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Department of Neurosurgery, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Biochem Biophys Rep. 2021 Mar 2;26:100958. doi: 10.1016/j.bbrep.2021.100958. eCollection 2021 Jul.
Maternal immune activation has been implicated in the pathophysiology of neurodevelopmental disorders such as autism spectrum disorders caused by maternal infection. It has been suggested that the placental origin of inflammatory cytokines leads to neurodevelopmental disorders. However, the identity of the initial immune-activated site in the placenta, in response to maternal viral infection, is not clear.
By cross-breeding male enhanced green fluorescent protein (EGFP) transgenic mice with wild-type females, the placental tissues of maternal origin can be distinguished from those of paternal origin by EGFP expression. Using this method, at embryonic day (E) 12.5, dams were administered an intraperitoneal polyriboinosinic-polyribocytidylic acid (poly [I:C]) injection. We quantitatively analyzed the levels of phosphorylated interferon (IFN) regulatory factor 3 (pIRF3) in the placenta, and investigated the distribution of pIRF3 positive cells.
We show that maternally derived decidual cells are the initial target of maternal poly (I:C) through the toll-like receptor 3/TIR-domain-containing the adapter-inducing interferon-β signaling pathway. We also show that the expression of interferon-β was upregulated in the placenta after maternal injection with poly (I:C).
These results suggest that maternally derived decidual cells are the initial target of maternal poly (I:C) and that this innate immune response is likely associated with a state of maternal immune activation.
母体免疫激活与神经发育障碍的病理生理学有关，如由母体感染引起的自闭症谱系障碍。有人提出，炎症细胞因子的胎盘来源会导致神经发育障碍。然而，胎盘对母体病毒感染作出反应时初始免疫激活位点的身份尚不清楚。
通过将雄性增强型绿色荧光蛋白（EGFP）转基因小鼠与野生型雌性小鼠杂交，可根据EGFP表达区分母体来源的胎盘组织和父体来源的胎盘组织。使用这种方法，在胚胎第12.5天，给孕鼠腹腔注射聚肌苷酸-聚胞苷酸（poly [I:C]）。我们定量分析了胎盘中磷酸化干扰素（IFN）调节因子3（pIRF3）的水平，并研究了pIRF3阳性细胞的分布。
我们发现，母体来源的蜕膜细胞是母体poly（I:C）通过Toll样受体3/TIR结构域衔接蛋白诱导干扰素-β信号通路的初始靶点。我们还发现，母体注射poly（I:C）后，胎盘中干扰素-β的表达上调。
这些结果表明，母体来源的蜕膜细胞是母体poly（I:C）的初始靶点，这种先天免疫反应可能与母体免疫激活状态有关。
