Toll-like receptors at the maternal-fetal interface in normal pregnancy and pregnancy disorders

Abstract

Toll-like receptors (TLR) form the major family of pattern recognition receptors (PRR) that are involved in innate immunity. Innate immune responses against microorganisms at the maternal-fetal interface may have a significant impact on the success of pregnancy, as intrauterine infections have been shown to be strongly associated with certain disorders of pregnancy. At the maternal-fetal interface, TLRs are expressed not only in the immune cells but also in non-immune cells such as trophoblasts and decidual cells; moreover, their expression patterns vary according to the stage of pregnancy. Here, we will describe potential functions of TLRs in these cells, their recognition and response to microorganisms, and their involvement in the innate immunity. The impact of TLR-mediated innate immune response will be discussed via animal model studies, as well as clinical observations.

Fig. 1

Toll-like receptor (TLR) signals. Membranal TLRs; TLR1, 2, 4, 5, 6, can recognize external signals, while cytoplasmic TLRs; TLR3, 7, 8, 9 will recognize intracellular signals. Following ligation, the majority of TLRs induce activation of NFκ B and cytokine production in MyD88-dependent manner. TLR4, like TLR3, can also signal in a MyD88-independent manner, which induces the expression of type I interferons (IFN) and IFN-inducible proteins. IFN, TRIF (Toll/IL-1 receptor domain-containing adaptor inducing IFN-β), IRF3 (IFN regulatory factor).

Fig. 2

Trophoblasts recognize viral component via TLR3 and respond by producing interferons and anti-microbial factors to control the viral attack (1). In addition, trophoblast produces cytokines and chemokines that will have a modulatory effect on the maternal immune system (2). Following bacterial infection, TLR2/TLR1 ligation in the trophoblast causes apoptosis, (3) while TLR2/TLR6 ligation or TLR4 ligation promotes cytokine production by trophoblasts (4). The inflammatory response initiated by trophoblast activates macrophages, NK cells and neutrophils for further immune modulation. (Modified from Koga and Mor 2008 Reproductive Sciences)