Impact of in vitro treatments of physiological levels of estradiol and progesterone observed in pregnancy on bovine monocyte-derived dendritic cell differentiation and maturation

Abstract

The specific factors which regulate differentiation and maturation of dendritic cells in bovine pregnancy remain unclear. We evaluated the influence of physiologically relevant in vitro treatments of progesterone (PG) and estradiol (E2) observed in late pregnancy on the differentiation and maturation of CD14+ monocyte-derived dendritic cell (moDC) from non-pregnant, lactating dairy cows (n=7). We found that moDC differentiated in the presence of both E2 and PG had impaired E. coli-induced phenotypic maturation, specifically a significant reduction in CD80 and MHC II expression. Contrary to our previous work characterizing moDC from late gestating dairy cattle, we did not observe an increase in CD14 expression relative to the untreated control; this increase was only observed in the current data in the dexamethasone-treated moDC. The moDC treated with a combination of both E2 and PG had significantly greater upregulation of anti-inflammatory cytokine IL-10 relative to the untreated control, but TNFα production was not suppressed; only dexamethasone-treated moDC showed abrogated TNFα production. These data suggest moDC may be regulated by E2 and PG to hinder phenotypic maturation and regulate inflammatory responses. Pregnancy-associated hormone profiles appear to be involved in the generation of maternal immune tolerance in pregnancy. These hormone-facilitated changes to moDC in pregnancy may also impede optimal immune responses to both invading pathogens and routine vaccinations administered in late gestation through limited antigen presentation and increased anti-inflammatory cytokine production. These results provide insight into maternal immune modulation and elucidate potential immune changes necessary to facilitate bovine pregnancy.

Effects of 17β-Estradiol on Monocyte/Macrophage Response to Staphylococcus aureus: An In Vitro Study

“…Levels of IL-10 mRNA in E2 treated MPMs from OVX females were significantly higher than those in MPMs from female sham and untreated OVX mice (Pepe et al, 2017). Pomeroy et al (2016) observed that bovine monocyte-derived dendritic cells (mDCs), stimulated with E. coli and treated with E2 and progesterone (PG) together, exhibited increased IL-10 production. However, treatment with either E2 or PG alone did not induce upregulation of IL-10.…”

Dendritic Cells and the Establishment of Fetomaternal Tolerance for Successful Human Pregnancy

“…When progesterone was added to the culture media for DCs, TNF-a expression was reduced, while the synthesis of Th2-skewing cytokines such as IL-10 was enhanced. This suggests that progesterone keeps DCs in an immature condition for immunological tolerance during pregnancy (Liang et al 2006;Xu et al 2011;Pomeroy et al 2016). E2 also regulates DC development as it was observed that nonsteroidal E2-antagonists prevent human monocytederived DCs from differentiating into functional DCs (Komi and Lassila 2000).…”