Aneman Ingrid, Pienaar Dillan, Suvakov Sonja, Simic Tatjana P, Garovic Vesna D, McClements Lana
Faculty of Science, School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia.
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States.
Front Immunol. 2020 Aug 18;11:1864. doi: 10.3389/fimmu.2020.01864. eCollection 2020.
Preeclampsia is a complex cardiovascular disorder of pregnancy with underlying multifactorial pathogeneses; however, its etiology is not fully understood. It is characterized by the new onset of maternal hypertension after 20 weeks of gestation, accompanied by proteinuria, maternal organ damage, and/or uteroplacental dysfunction. Preeclampsia can be subdivided into early- and late-onset phenotypes (EOPE and LOPE), diagnosed before 34 weeks or from 34 weeks of gestation, respectively. Impaired placental development in early pregnancy and subsequent growth restriction is often associated with EOPE, while LOPE is associated with maternal endothelial dysfunction. The innate immune system plays an essential role in normal progression of physiological pregnancy and fetal development. However, inappropriate or excessive activation of this system can lead to placental dysfunction or poor maternal vascular adaptation and contribute to the development of preeclampsia. This review aims to comprehensively outline the mechanisms of key innate immune cells including macrophages, neutrophils, natural killer (NK) cells, and innate B1 cells, in normal physiological pregnancy, EOPE and LOPE. The roles of the complement system, syncytiotrophoblast extracellular vesicles and mesenchymal stem cells (MSCs) are also discussed in the context of innate immune system regulation and preeclampsia. The outlined molecular mechanisms, which represent potential therapeutic targets, and associated emerging treatments, are evaluated as treatments for preeclampsia. Therefore, by addressing the current understanding of innate immunity in the pathogenesis of EOPE and LOPE, this review will contribute to the body of research that could lead to the development of better diagnosis, prevention, and treatment strategies. Importantly, it will delineate the differences in the mechanisms of the innate immune system in two different types of preeclampsia, which is necessary for a more personalized approach to the monitoring and treatment of affected women.
子痫前期是一种复杂的妊娠心血管疾病，其发病机制具有多因素性；然而，其病因尚未完全明确。其特征是妊娠20周后孕妇新发高血压，并伴有蛋白尿、母体器官损害和/或子宫胎盘功能障碍。子痫前期可分为早发型和晚发型（早发型子痫前期和晚发型子痫前期），分别在妊娠34周前或妊娠34周后诊断。妊娠早期胎盘发育受损及随后的生长受限常与早发型子痫前期相关，而晚发型子痫前期则与母体血管内皮功能障碍有关。先天免疫系统在生理妊娠和胎儿发育的正常进程中起着至关重要的作用。然而，该系统的不适当激活或过度激活会导致胎盘功能障碍或母体血管适应性不良，并促使子痫前期的发生。本综述旨在全面概述关键先天免疫细胞（包括巨噬细胞、中性粒细胞、自然杀伤细胞和先天B1细胞）在正常生理妊娠、早发型子痫前期和晚发型子痫前期中的作用机制。还将在先天免疫系统调节和子痫前期的背景下讨论补体系统、合体滋养层细胞外囊泡和间充质干细胞的作用。所概述的分子机制代表了潜在的治疗靶点，并对相关的新兴治疗方法进行了评估，作为子痫前期的治疗手段。因此，通过阐述目前对早发型子痫前期和晚发型子痫前期发病机制中先天免疫的理解，本综述将有助于推动相关研究，从而开发出更好的诊断、预防和治疗策略。重要的是，它将阐明先天免疫系统在两种不同类型子痫前期中的机制差异，这对于更个性化地监测和治疗受影响的女性是必要的。
