Monocytes and macrophages in pregnancy: The good, the bad, and the ugly

A successful human pregnancy requires precisely timed adaptations by the maternal immune system to support fetal growth while simultaneously protecting mother and fetus against microbial challenges. The first trimester of pregnancy is characterized by a robust increase in innate immune activity that promotes successful implantation of the blastocyst and placental development. Moreover, early pregnancy is also a state of increased vulnerability to vertically transmitted pathogens notably, human immunodeficiency virus (HIV), Zika virus (ZIKV), SARS-CoV-2, and Listeria monocytogenes. As gestation progresses, the second trimester is marked by the establishment of an immunosuppressive environment that promotes fetal tolerance and growth while preventing preterm birth, spontaneous abortion, and other gestational complications. Finally, the period leading up to labor and parturition is characterized by the reinstatement of an inflammatory milieu triggering childbirth. These dynamic waves of carefully orchestrated changes have been dubbed the "immune clock of pregnancy." Monocytes in maternal circulation and tissue-resident macrophages at the maternal-fetal interface play a critical role in this delicate balance. This review will summarize the current data describing the longitudinal changes in the phenotype and function of monocyte and macrophage populations in healthy and complicated pregnancies.