TY - JOUR
T1 - Functional and genomic adaptations of blood monocytes to pregravid obesity during pregnancy
AU - Sureshchandra, Suhas
AU - Marshall, Nicole E.
AU - Mendoza, Norma
AU - Jankeel, Allen
AU - Zulu, Michael Z.
AU - Messaoudi, Ilhem
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/6/25
Y1 - 2021/6/25
N2 - Pregravid 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.
AB - Pregravid 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.
KW - Immune system
KW - Immunology
KW - Pregnancy
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U2 - 10.1016/j.isci.2021.102690
DO - 10.1016/j.isci.2021.102690
M3 - Article
AN - SCOPUS:85108174212
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 6
M1 - 102690
ER -