Cell-type specific distribution and activation of type I IFN pathway molecules at the placental maternal-fetal interface in response to COVID-19 infection.
Cell-type specific distribution and activation of type I IFN pathway molecules at the placental maternal-fetal interface in response to COVID-19 infection.
复制标题
细胞类型的特异性分布和I型IFN途径分子在胎盘母亲界面上的激活，响应于19 covid-19的感染。
DOI：
10.3389/fendo.2022.951388
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
孕期感染新冠肺炎可显著增加不良妊娠结局的风险。然而，胎盘母胎界面的先天免疫对新冠肺炎感染有何反应，目前知之甚少。I型干扰素细胞因子被认为是对抗病毒感染的先天免疫反应的关键组成部分。在这项研究中，我们特异性地评估了妊娠期间感染新冠肺炎的妇女胎盘中干扰素抗病毒信号分子的表达。用免疫组织化学方法检测了福尔马林固定石蜡包埋的胎盘组织(绒毛和胎膜)中干扰素活化信号通路分子环磷酸腺苷合成酶(CGAS)、干扰素基因刺激因子(STING)、干扰素调节因子3(IRF3)、Toll样受体7(TLR7)、线粒体抗病毒信号蛋白(MAVS)和干扰素β的表达。总共检查了20个胎盘，其中12个来自新冠肺炎患者，8个来自非新冠肺炎对照组。患者的人口统计学、临床数据和胎盘病理报告是通过EPIC病历回顾获得的。除BMI和胎盘重量外，COVID组和非COVID组在母亲年龄、分娩时孕周、重力/产次、分娩方式、新生儿性别和体重方面均无统计学差异。在COVID暴露组，胎盘盘的主要病理特征是母体和胎儿的血管灌注不良和慢性炎症。与非COVID对照组相比，COVID暴露的胎盘组织中，干扰素活化途径分子的表达均上调，并且具有不同的细胞类型特异性分布：绒毛和蜕膜基质细胞中的刺状细胞；细胞滋养层细胞(CTs)和绒毛外滋养层细胞(EVT)中的IRF3；合体滋养层细胞(STS)、CTs和EVT中的TLR7和MAVS。在胎儿内皮细胞中，STING、MAVS和TLR7的表达也有上调。SING、IRF3、TLR7和MAV是调节I型干扰素产生的关键病毒传感分子。I型干扰素是一种有效的抗病毒细胞因子，可以削弱和根除感染细胞中的病毒复制。这些先天抗病毒分子在胎盘母胎界面的细胞类型特异性分布和激活的发现，为I型干扰素途径分子可能在胎盘抗SARS-CoV-2感染中发挥关键作用提供了可信的证据。我们的发现还表明，胎盘母胎界面具有明确的抗病毒防御系统，以保护发育中的胎儿免受SARS-CoV-2感染。
COVID-19 infection in pregnancy significantly increases risks of adverse pregnancy outcomes. However, little is known how the innate immunity at the placental maternal-fetal interface responds to COVID-19 infection. Type I IFN cytokines are recognized as a key component of the innate immune response against viral infection. In this study, we specifically evaluated expression of IFN antiviral signaling molecules in placentas from women infected with COVID-19 during pregnancy. Expression of IFN activation signaling pathway molecules, including cyclic GMP–AMP synthase (cGAS), stimulator of interferon genes (STING), interferon regulatory factor 3 (IRF3), Toll-like receptor 7 (TLR7), mitochondrial antiviral-signaling protein (MAVS), and IFNβ were determined in formalin-fixed paraffin embedded (FFPE) placental tissue sections (villous and fetal membrane) by immunostaining. A total of 20 placentas were examined, 12 from COVID-19 patients and 8 from non-COVID-19 controls. Patient demographics, clinical data, and placental pathology report were acquired via EPIC medical record review. Except BMI and placental weight, there was no statistical difference between COVID and non-COVID groups in maternal age, gestational age at delivery, gravity/parity, delivery mode, and newborn gender and weight. In COVID-exposed group, the main pathological characteristics in the placental disc are maternal and fetal vascular malperfusion and chronic inflammation. Compared to non-COVID controls, expression of IFN activation pathway molecules were all upregulated with distinct cell-type specific distribution in COVID-exposed placentas: STING in villous and decidual stromal cells; IRF3 in cytotrophoblasts (CTs) and extra-villous trophoblasts (EVTs); and TLR7 and MAVS in syncytiotrophoblasts (STs), CTs, and EVTs. Upregulation of STING, MAVS and TLR7 was also seen in fetal endothelial cells. STING, IRF3, TLR7, and MAVS are key viral sensing molecules that regulate type I IFN production. Type I IFNs are potent antiviral cytokines to impair and eradicate viral replication in infected cells. The finding of cell-type specific distribution and activation of these innate antiviral molecules at the placental maternal-fetal interface provide plausible evidence that type I IFN pathway molecules may play critical roles against SARS-CoV-2 infection in the placenta. Our findings also suggest that placental maternal-fetal interface has a well-defined antiviral defense system to protect the developing fetus from SARS-CoV-2 infection.
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影响因子：
7.3
作者：
Rebutini PZ;Zanchettin AC;Stonoga ETS;Prá DMM;de Oliveira ALP;Dezidério FDS;Fonseca AS;Dagostini JCH;Hlatchuk EC;Furuie IN;Longo JDS;Cavalli BM;Dino CLT;Dias VMCH;Percicote AP;Nogueira MB;Raboni SM;de Carvalho NS;Machado-Souza C;de Noronha L
通讯作者：
de Noronha L
影响因子：
5.8
作者：
Moreno-Eutimio, Mario Adan;Lopez-Macias, Constantino;Pastelin-Palacios, Rodolfo
通讯作者：
Pastelin-Palacios, Rodolfo
影响因子：
30.3
作者：
Arora N;Sadovsky Y;Dermody TS;Coyne CB
通讯作者：
Coyne CB
影响因子：
4.9
作者：
Hoogduijn MJ
通讯作者：
Hoogduijn MJ
DOI：
10.3389/fviro.2022.813312
发表时间：
2022-02-08
期刊：
FRONTIERS IN VIROLOGY
影响因子：
--
作者：
Sharps, Megan C.;Garrod, Ainslie;Heazell, Alexander E. P.
通讯作者：
Heazell, Alexander E. P.