No abstract

Pre-pregnancy obesity is associated with several adverse maternal health outcomes, notably increased risk of infection as well as the incidence of gestational diabetes, preeclampsia, and preterm birth. However, the mechanisms by which pregravid obesity disrupts the pregnancy associated “immune clock” are still unknown. To address this question, we collected blood samples from women during the first and third trimesters and determined the impact of both pregnancy and pregravid obesity on circulating immune mediators, immune cell subset frequencies, and peripheral immune responses. While regardless of BMI, pregnancy was associated with an elevation in both Th1 and Th2 cytokines, pregravid obesity was associated with a dysregulation in circulating myeloid factors at term. Moreover, pregnancy in lean subjects was associated with enhanced monocyte activation, augmented chromatin accessibility at inflammatory loci, and heightened responses to LPS. Pregravid obesity disrupted this trajectory and was accompanied by a lack of transcriptional and epigenetic changes and alterations in metabolic status strongly suggesting a skewing towards immunotolerance. These findings provide novel insight into the increased susceptibility to infections observed with obesity during pregnancy.SUMMARYA healthy pregnancy is associated with progressive innate immune activation. Maternal factors such as obesity compromise this myeloid cell activation trajectory at genomic, epigenomic, functional, and metabolic levels, resulting in stagnant immune responses, suggestive of a state of tolerance.

No abstract

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.