The role of the Nod-like receptor family in trophoblast innate immune responses

There is a strong clinical association between intrauterine infections and pregnancy complications, such as preterm labor. The placenta functions as an active barrier whereby the trophoblast recognizes microbes through pattern recognition receptors, such as the well characterized Toll-like receptors, in order to respond to pathogens at the maternal-fetal interface. Consequently, either an inefficient or overactive placental response to an infectious trigger, may have a significant impact on pregnancy outcome. Recently the placenta has been shown to express a newly identified family of pattern recognition receptors, the cytoplasmic-based Nod-like receptors (NLRs). As a result of their restricted localization, NLRs function as intracellular receptors that respond to infectious components, which have gained access to the cytoplasmic compartment. Thus, NLRs may provide the trophoblast with a recognition system that may be critical in placental responses to microorganisms or their cell wall components that have gained access to the cell's intracellular space, or that have evaded recognition by the TLRs. This review will discuss what is currently known about the role of NOD proteins, NALP proteins, and the inflammasome at the maternal-fetal interface, and their potential role in infection-associated pregnancy complications, like preterm labor. As we learn more about their function at the maternal-fetal interface, we will have a better understanding of their function in normal pregnancy and their potential to contribute to the pathogenesis of infection- and inflammation-associated pregnancy complications.