Abstract
SummaryPregravid obesity is associated with several adverse maternal health outcomes, such as increased risk of infection, suggesting an altered immunological state. However, the mechanisms by which obesity disrupts the pregnancy “immune clock” are still unknown. Here, we profiled circulating immune mediators, immune cell subset frequencies, and peripheral immune responses during the first and third trimesters of pregnancy in lean and obese mothers. While both Th1 and Th2 cytokines were elevated with pregnancy regardless of BMI, obese subjects had dysregulated myeloid factors in circulation at term. 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, resulting in a lack of transcriptional, epigenetic, and metabolic changes strongly suggesting a skewing toward innate immune tolerance. These findings provide novel insight into the increased susceptibility to infections in women with obesity during pregnancy and following cesarean delivery.
Highlights
The maternal immune system undergoes several fine-tuned adaptations throughout pregnancy dubbed the ‘‘immunological clock of pregnancy’’ (Mor and Cardenas, 2010)
SUMMARY Pregravid obesity is associated with several adverse maternal health outcomes, such as increased risk of infection, suggesting an altered immunological state
Pregnancy in lean subjects was associated with enhanced monocyte activation, augmented chromatin accessibility at inflammatory loci, and heightened responses to LPS
Summary
The maternal immune system undergoes several fine-tuned adaptations throughout pregnancy dubbed the ‘‘immunological clock of pregnancy’’ (Mor and Cardenas, 2010) These adaptations are believed to facilitate implantation, fetal tolerance, fetal growth and development, and labor and parturition without compromising protection against microbial infections (Mor et al, 2011). These changes do not necessarily follow waves of pro- and anti-inflammatory phases (Mor and Cardenas, 2010), but rather a progressive activation of signaling molecules (Aghaeepour et al, 2017) and alterations in the circulating proteome (Aghaeepour et al, 2018). The precise mechanisms underlying this progressive activation of the innate immune branch remain poorly defined
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