The human placenta shapes the phenotype of decidual macrophages

During human pregnancy, placenta-derived extravillous trophoblasts (EVTs) invade the decidua and communicate 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 (decPAMs). 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 characterized by induced expression of HLA class II molecules, enhanced phagocytosis, and the ability to activate 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. [Display omitted] •Decidua basalis-associated macrophages (decBAMs) accumulate during human pregnancy•decBAMs are CD11c+HLA-DRlo, have a specific transcriptome, and proliferate in situ•decBAMs are inefficient APCs, induce Tregs, and secrete IL-10 and M-CSF•Invasive trophoblasts induce a decBAM-associated phenotype Vondra et al. report the accumulation of CD163+CD206+CD11chiHLA-DRlo macrophages termed decidua basalis-associated macrophages (decBAMs). decBAMs proliferate, secrete pregnancy-sustaining factors, and induce Tregs but show diminished phagocytosis and T cell activation efficiency. The secretome of placenta-derived trophoblasts partly induces this phenotype, suggesting that placentation co-regulates macrophage polarization during human pregnancy.