Innate and Adaptive Immune Interactions at the Fetal–Maternal Interface in Healthy Human Pregnancy and Pre-Eclampsia

Abstract

Maternal immune tolerance of the fetus is indispensable for a healthy pregnancy outcome. Nowhere is this immune tolerance more important than at the fetal–maternal interface – the decidua, the site of implantation, and placentation. Indeed, many lines of evidence suggest an immunological origin to the common pregnancy-related disorder, pre-eclampsia. Within the innate immune system, decidual NK cells and antigen presenting cells (including dendritic cells and macrophages) make up a large proportion of the decidual leukocyte population, and are thought to modulate vascular remodeling and trophoblast invasion. On the other hand, within the adaptive immune system, Foxp3+ regulatory T cells are crucial for ensuring immune tolerance toward the semi-allogeneic fetus. Additionally, another population of CD4+HLA-G+ suppressor T cells has also been identified as a potential player in the maintenance of immune tolerance. More recently, studies are beginning to unravel the potential interactions between the innate and the adaptive immune system within the decidua, that are required to maintain a healthy pregnancy. In this review, we discuss the recent advances exploring the complex crosstalk between the innate and the adaptive immune system during human pregnancy.

Preeclampsia and health risks later in life: an immunological link

“…Severity of preeclampsia pathology is also a leading cause of preterm birth. Thus, if an altered immune system contributes to the systemic and local symptoms of preeclampsia [11][12][13][14][15][16][17][18][19][20][21][22], it is tempting to speculate that the same or diverse underlying immune changes may predispose to different phenotypes of the syndrome. Dysregulation of immunity in preeclampsia is thought to start with inadequate immune tolerance to paternal alloantigens present on trophoblasts.…”

“…Nevertheless, recent data suggest that the defective immune intolerance to the conceptus may be involved through primary and secondary immune responses. Although a considerable number of reviews have already focused on different aspects of immune responses including the role of macrophages in preeclampsia [11][12][13][14][15][16][17][18][19][20][21][22], this review will provide contemporary discussion on NK cells and regulatory T cells (Tregs) and their participation in the pathology of this pregnancy complication. A focus on NK cells and Tregs can be rationalized because NK cells predominantly populate the pregnant uterus and guide trophoblast invasion whereas Tregs are recruited to the endometrium in response to hormones to establish immune tolerance.…”

Critical Role and Therapeutic Control of the Lectin Pathway of Complement Activation in an Abortion-Prone Mouse Mating

“…This is a unique physiologic condition, which requires adaptation of the immune system to avoid harming the fetoplacental unit and to ensure regular progression of pregnancy. The adaptive and the innate arms of the immune system are both involved in this process and develop strategies to establish a protective environment in maternal decidua to prevent fetal demise (1). C is a humoral component of innate immunity, which fulfills protective functions providing a critical defense barrier against infectious agents potentially harmful to the fetus (2,3).…”

Periostin and implantation: a new biomarker of embryo-endometrial cross talk

“…At the same time, many authors investigated the role of the immune system in the embryo implantation (10,71), however in the current literature no direct data about the potential role of POSTN in modulating the immune response and inflammation at implantation are available. Several data indicate that POSTN and other ECM proteins, including OPN and osteonectin, play an important role in the creation of permissive microenvironment in different inflammatory diseases (airway and skin inflammation, atherosclerosis and fibrosis) and in tumors (70,(72)(73)(74)(75).…”