A new study shows alterations in placental macrophage activation and in their interactions with trophoblasts in women with pre-eclampsia. Przybyl et al. report a significant reduction in CD74+ placental macrophages in pre-eclamptic women compared with healthy controls. Macrophages that lacked CD74 showed reductions in adhesion molecule expression and trophoblast adherence as well as a shift towards a pro-inflammatory signature when co-cultured with trophoblasts. In mice, CD74 knockout resulted in placental abnormalities and fetal growth restriction.