The human placenta shapes the phenotype of decidual macrophages

During human pregnancy, placenta-derived extravillous trophoblasts (EVTs) invade the decidua and commu-nicate with maternal immune cells. The decidua distinguishes into basalis (decB) and parietalis (decP). The latter remains unaffected by EVT invasion. By defining a specific gating strategy, we report the accumulation of macrophages in decB. We describe a decidua basalis-associated macrophage (decBAM) population with a differential transcriptome and secretome compared with decidua parietalis-associated macrophages (dec-PAMs). decBAMs are CD11chi and efficient inducers of Tregs, proliferate in situ, and secrete high levels of CXCL1, CXCL5, M-CSF, and IL-10. In contrast, decPAMs exert a dendritic cell-like, motile phenotype char-acterized by induced expression of HLA class II molecules, enhanced phagocytosis, and the ability to acti-vate T cells. Strikingly, EVT-conditioned media convert decPAMs into a decBAM phenotype. These findings assign distinct macrophage phenotypes to decidual areas depending on placentation and further highlight a critical role for EVTs in the induction of decB-associated macrophage polarization.Funding Agencies|Clinical biomarker facility at SciLifeLab Sweden; Austrian Science Fund [P33485]; Austrian National Bank [17613ONB]</p