Mechanisms of Key Innate Immune Cells in Early- and Late-Onset Preeclampsia.

Ingrid Aneman,Tatjana P Simic,Lana Mcclements,Vesna D Garovic,Sonja Suvakov,Dillan Pienaar

doi:10.3389/fimmu.2020.01864

Abstract

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.

Highlights

Preeclampsia accounts for over 70,000 maternal and 500,000 fetal/neonatal deaths annually, with maternal deaths being highest in developing countries [1, 2]
We will outline mechanisms of key innate immune cells implicated in the development of preeclampsia and differentiate how these mechanisms are affected in two phenotypes of preeclampsia, early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE)
This, in conjunction with the ability of certain placental cells to modulate the immune system, confers a level of protection to the developing fetus against detrimental immunological responses. This delicate balance is disrupted in preeclampsia, leading to the inappropriate over-activation of these immune cells, causing disruption of appropriate placentation and contributing to the development of this hypertensive condition with end-organ damage

Summary

Introduction

Preeclampsia accounts for over 70,000 maternal and 500,000 fetal/neonatal deaths annually, with maternal deaths being highest in developing countries [1, 2]. The exact etiology of preeclampsia is unknown, endothelial dysfunction, inappropriate angiogenesis, inadequate trophoblast invasion and spiral uterine artery remodeling, have all been identified as key contributors [3,4,5,6]. Adequate remodeling of spiral uterine arteries into dilated, elastic, and low-resistance blood vessels enables unlimited supplies of oxygen and nutrients to the fetus. This requires appropriate invasion by extravillous trophoblasts and replacement of maternal endothelial cells [7]. We will outline mechanisms of key innate immune cells implicated in the development of preeclampsia and differentiate how these mechanisms are affected in two phenotypes of preeclampsia, early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE). EOPE is diagnosed before 34 weeks of gestation whereas LOPE is diagnosed from 34 weeks of gestation [2]

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