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

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.

Innate Immune Responses to Acute Viral Infection During Pregnancy

“…This reflects a state of enhanced innate immune vigilance against infection: neutrophils, the most abundant of all human phagocytes, are recruited to sites of infection or injury by chemokines such as complement C5a and form the first line of defense against microbial challenge. Engulfed micro-organisms are internalized in phagolysosomes and destroyed using a wide range of effector mechanisms including release of serine proteases (e.g., neutrophil elastase, cathepsin G) and production of reactive oxygen species (141,169). Pathogens that evade phagocytosis can be controlled by the release of neutrophil extracellular traps (NET), large reticular structures containing cytotoxic granule proteins and AMP that sequester and neutralize microbes (170).…”

“…Decidual DC (dDC) account for <2% of decidual leukocytes, are a highly proliferative and relatively immature population, and are phenotypically distinct from peripheral DC: they display a universal reduction in expression of T cell costimulatory molecules and thus fail to induce specific T cell responses in vitro (189). dDC help to prevent fetal rejection by promoting tolerogenic responses to endocytosed trophoblast antigens, recruit NK cells through production of IL-15 and potentiate decidual angiogenesis via close dialogue with decidual stromal cells (141).…”

Toll-like receptor 3 -926T>A increased the risk of breast cancer through decreased transcriptional activity

“…Toll-like receptors (TLRs) are important regulators in both the adaptive and innate immune responses. [10][11][12] They are capable of inducing antitumor mediators and are highly expressed on antigen-presenting cells. TLRs selectively recognize a variety of conserved molecular structures in invading pathogens.…”

Human Chorionic Gonadotropin-Mediated Immune Responses That Facilitate Embryo Implantation and Placentation

“…During the first trimester of pregnancy NK cells represent the most abundant immune cell population in decidual tissue (105). However, whether decidual NK cells are derived from peripheral NK cells that enter the fetal-maternal interface and convert into the decidual phenotype and/or expand from residual NK cells is not finally resolved (106,107). Recently, it was suggested that under the influence of P4 and IL-15, peripheral NK cells start to proliferate, migrate into the implantation site along chemotactic and hormonal gradients provided by trophoblast and endometrial cells and finally convert into decidual NK cells due to high levels of local TGF-β and IL-11 (106).…”