Innate Immune Cells and Toll-like Receptor-Dependent Responses at the Maternal-Fetal Interface.

Pilar Flores-Espinosa,Ismael Mancilla-Herrera,Verónica Zaga-Clavellina,Andrea Olmos-Ortiz,Rodrigo Vega-Sánchez,Lorenza Díaz

doi:10.3390/ijms20153654

Abstract

During pregnancy, the placenta, the mother and the fetus exploit several mechanisms in order to avoid fetal rejection and to maintain an immunotolerant environment throughout nine months. During this time, immune cells from the fetal and maternal compartments interact to provide an adequate defense in case of an infection and to promote a tolerogenic milieu for the fetus to develop peacefully. Trophoblasts and decidual cells, together with resident natural killer cells, dendritic cells, Hofbauer cells and other macrophages, among other cell types, contribute to the modulation of the uterine environment to sustain a successful pregnancy. In this review, the authors outlined some of the various roles that the innate immune system plays at the maternal–fetal interface. First, the cell populations that are recruited into gestational tissues and their immune mechanisms were examined. In the second part, the Toll–like receptor (TLR)–dependent immune responses at the maternal–fetal interface was summarized, in terms of their specific cytokine/chemokine/antimicrobial peptide expression profiles throughout pregnancy.

Highlights

In this review, the importance of the involvement of innate immune cells in implantation, decidual–stromal interaction, angiogenesis and fetal growth was emphasized
During the first trimester of pregnancy, peripheral NK (pNK) cells represent approximately 5–30% of circulating leukocytes, whereas Decidual NK (dNK) cells comprise 70% of decidual leukocytes [7,18]; the other 30% being composed of macrophages and T–cells [17]
The main factor involved in their differentiation is the macrophage–colony stimulating factor (M-CSF), plus other mediators that vary depending on the specific type of macrophages being generated

Summary

Innate Cell Populations at the Maternal–Fetal Interface

Pregnancy represents a temporal state in which the harmonic development of the fetus depends on a delicate balance between anatomic, endocrine, metabolic and immune factors. Immune tolerance to the fetal semi-allograft depends on specific changes within the mother’s reproductive tract aimed at avoiding fetal rejection by the maternal immune system, while maintaining a functional defensive response against pathogens [1]. This tolerogenic state is well established since early pregnancy, especially within those maternal and fetal tissues that are in direct contact with each other, i.e., villous trophoblasts in contact with maternal blood immune cells, and chorioamniotic membranes overlying the maternal decidual layer. A section on Toll-like receptor (TLR)–mediated responses was included to show their pathogen– tissue and temporal–specific immune mechanisms during pregnancy

Natural Killer Cells

Macrophages

Dendritic Cells

Neutrophils

Toll-Like Receptors

TLRs During Pregnancy

Findings

Summary