Peripheral Monocyte Expression of the Chemokine Receptors CCR2, CCR5 and CXCR3 is Altered at Parturition in Healthy Women and in Women with Systemic Lupus Erythematosus

Abstract

Monocytes are precursors of macrophages and recruited to the uterus throughout pregnancy to perform important immunological functions. In this study, we hypothesized that pregnant women have reduced peripheral monocyte expression of chemokine receptors and alterations in PBMC responses to microbial stimuli as an adaption to pregnancy and that these changes are less pronounced in women with autoimmunity. We therefore investigated the chemokine receptor expression, migratory behaviour and responses to microbial stimulation of peripheral monocytes from pregnant women at parturition (n = 13) and from non-pregnant women (n = 9). In addition, we compared healthy pregnant women with women suffering from SLE (n = 5), a condition with pronounced systemic inflammation increasing the risk for pregnancy complications. We demonstrate that peripheral monocytes are affected by pregnancy with reduced percentages of CCR2+, CCR5+ and CXCR3+ monocytes of both classical (CD16-) and inflammatory (CD16+) subsets and that the trophoblast-secreted chemokine CCL2/MCP-1 recruited monocytes of both subsets in vitro. Further, PBMCs from pregnant women had a divergent response to microbial stimulation with lower CCL5/RANTES and higher CCL2/MCP-1 secretion compared with non-pregnant women. In addition, pregnant women had lower basal PBMC-secretion of CCL5/RANTES and higher basal secretion of IL-10 and CCL2/MCP-1. Interestingly, the women with SLE responded similar to pregnancy as did healthy women with lower percentages of CCR2+, CCR5+ and CXCR3+ monocytes. However, they had increased expression of CCR5 on CD16+ monocytes and heightened PBMC-secretion of CCL5/RANTES. In conclusion, our data indicate that monocyte chemokine receptor expression and the chemokine milieu during pregnancy are tightly regulated to support pregnancy.