Features of Human Decidual NK Cells in Healthy Pregnancy and During Viral Infection

Abstract

The hallmark of human early pregnancy is the accumulation of a unique population of Natural Killer (dNK) cells at the main maternal-fetal interface, the decidua basalis . dNK cells play a crucial role in successful placentation probably by orchestrating the invasion of trophoblast cells deep into the decidua basalis and remodeling of the maternal spiral arteries. Recent advances in the field emphasize the importance of the local microenvironment in shaping both the phenotype and the effector functions of these innate lymphoid cells. Despite slow progress in the field, ex vivo studies revealed that dNK cells sense and destroy infected cells in order to protect the fetus from invading pathogens. In this review, we will discuss key features of dNK cells during healthy pregnancy as well as their functional adaptations in limiting pathogen dissemination to the growing conceptus. The challenge is to better understand the plasticity of dNK cells in the maternal-fetal interface. Such insights would enable greater understanding of the pathogenesis in congenital infections and pregnancy disorders.

The Unique Microbiome and Innate Immunity During Pregnancy

“…Mandelboim et al discovered further that some virus-infected cells might be recognized by the NKp46 receptor through the binding of viral hemaglutinin, inducing a rise of intracellular calcium mobilization, perforin polarization, granule exocytosis, and efficient target cell lysis (109). Meantime, the study has proven that if the dNK cells are exposed to HCMV, it may happen with phenotypic changes and the acquisition of a cytotoxic function involving the NKG2D activating receptors (similar to NKp46) to prevent viral spread and placental pathology (110). dNK cells can not only prevent congenital HCMV infection by reducing the secretion of relative to trophoblast invasion such as CCL2, CCL4, CCL5, CXCL10, granulocyte-macrophage colony-stimulating factor, and CXCL8 but also activate other immune cells, namely, T cells (111).…”

Innate Immune Responses to Acute Viral Infection During Pregnancy

“…These receptors signal via mitochondrial antiviral-signaling protein (MAVS) and IRF3/7, culminating in a second wave of type I IFN production (91,95) (Figure 3). The emerging role of NK cells in antiviral immunity and pregnancy, recently reviewed in this journal (66), has provoked controversy and is discussed in more detail below.…”

“…TLR expression at the maternal-fetal interface exhibits both temporal and tissue-specific fluctuations in expression levels and functionality (131)(132)(133)(134). This suggests a potential contribution to the observed differences in severity of fetal and maternal viral infections in different trimesters (42,44,48,66,135). In human trophoblast, TLR3 is highly abundant in the first trimester and forms a defensive barrier along the cytotrophoblast with TLR2 and TLR4 (136).…”

Maternal-Fetal Interplay in Zika Virus Infection and Adverse Perinatal Outcomes

“…dNK cells represent ∼70% of the leukocytes present in the decidua during the first trimester of pregnancy and have a crucial role during placentation (23,25), acting with trophoblastic cells (cytotrophoblasts, syncytiotrophoblast, and extravillous trophoblasts) during this process (26). The plasticity of dNK cells is crucial for successful pregnancy, and while these cells are important for orchestrating the invasion of trophoblast cells and spiral artery remodeling, they also protect the fetus from pathogens by destroying infected cells (26).…”