Girsch James H, Mejia Plazas Maria C, Olivier Amanda, Farah Mohamed, Littlefield Dawn, Behl Supriya, Punia Sohan, Sakemura Reona, Hemsath Jack R, Norgan Andrew, Enninga Elizabeth A L, Johnson Erica L, Chakraborty Rana
Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN, United States.
Mayo Clinic Graduate School of Biomedical Science, Rochester, MN, United States.
Frontiers (Boulder). 2022 Mar;2. doi: 10.3389/fviro.2022.833106. Epub 2022 Mar 24.
In humans, the hemochorial placenta is a unique temporary organ that forms during pregnancy to support fetal development, gaseous exchange, delivery of nutrition, removal of waste products, and provides immune protection, while maintaining tolerance to the HLA-haploidentical fetus. In this review, we characterize decidual and placental immunity during maternal viral (co)-infection with HIV-1, human cytomegalovirus (HCMV), and Zika virus. We discuss placental immunology, clinical presentation, and epidemiology, before characterizing host susceptibility and cellular tropism, and how the three viruses gain access into specific placental target cells. We describe current knowledge on host-viral interactions with decidual and stromal human placental macrophages or Hofbauer cells, trophoblasts including extra villous trophoblasts, T cells, and decidual natural killer (dNK) cells. These clinically significant viral infections elicit both innate and adaptive immune responses to control replication. However, the three viruses either during mono- or co-infection (HIV-1 and HCMV) escape detection to initiate placental inflammation associated with viral transmission to the developing fetus. Aside from congenital or perinatal infection, other adverse pregnancy outcomes include preterm labor and spontaneous abortion. In addition, maternal HIV-1 and HCMV co-infection are associated with impaired fetal and infant immunity in postnatal life and poor clinical outcomes during childhood in exposed infants, even in the absence of vertical transmission of HIV-1. Given the rapidly expanding numbers of HIV-1-exposed uninfected infants and children globally, further research is urgently needed on neonatal immune programming during maternal mono-and co-infection. This review therefore includes sections on current knowledge gaps that may prompt future research directions. These gaps reflect an emerging but poorly characterized field. Their significance and potential investigation is underscored by the fact that although viral infections result in adverse consequences in both mother and developing fetus/newborn, antiviral and immunomodulatory therapies can improve clinical outcomes in the dyad.
在人类中，血绒毛膜胎盘是一种独特的临时器官，在怀孕期间形成以支持胎儿发育、气体交换、营养输送、废物清除，并提供免疫保护，同时维持对HLA单倍型相同胎儿的耐受性。在本综述中，我们描述了孕妇在感染HIV-1、人类巨细胞病毒（HCMV）和寨卡病毒时蜕膜和胎盘的免疫情况。在描述宿主易感性和细胞嗜性以及这三种病毒如何进入特定胎盘靶细胞之前，我们讨论了胎盘免疫学、临床表现和流行病学。我们阐述了目前关于宿主与病毒在蜕膜和基质中的人胎盘巨噬细胞或霍夫鲍尔细胞、滋养层细胞（包括绒毛外滋养层细胞）、T细胞和蜕膜自然杀伤（dNK）细胞之间相互作用的知识。这些具有临床意义的病毒感染引发先天性和适应性免疫反应以控制病毒复制。然而，这三种病毒在单一感染或合并感染（HIV-1和HCMV）期间都会逃避检测，从而引发与病毒传播给发育中的胎儿相关的胎盘炎症。除了先天性或围产期感染外，其他不良妊娠结局还包括早产和自然流产。此外，即使没有HIV-1的垂直传播，孕妇HIV-1和HCMV合并感染也与出生后胎儿和婴儿免疫功能受损以及暴露婴儿儿童期不良临床结局有关。鉴于全球范围内暴露于HIV-1但未感染的婴儿和儿童数量迅速增加，迫切需要进一步研究孕妇单一感染和合并感染期间的新生儿免疫编程。因此，本综述包括了关于当前知识空白的章节，这些空白可能会促使未来的研究方向。这些空白反映了一个新兴但特征尚不明确的领域。尽管病毒感染会给母亲和发育中的胎儿/新生儿都带来不良后果，但抗病毒和免疫调节疗法可以改善母婴双方的临床结局，这一事实凸显了它们的重要性和潜在研究价值。
