The immunophenotype of decidual macrophages in acute atherosis

PROBLEM: Acute atherosis is a uteroplacental arterial lesion that is associated with pregnancy complications such as preeclampsia and preterm birth, the latter being the leading cause of perinatal morbidity and mortality worldwide. However, the immunobiology of acute atherosis is poorly understood. METHOD OF STUDY: Placental basal plate samples were collected from women who delivered with (n = 11) and without (n = 31) decidua basalis lesions of acute atherosis. Multicolor flow cytometry was used to quantify M1- and M2-like macrophage subsets and the expression of iNOS and IL-12 by decidual macrophages. Multiplex fluorescence staining and phenoptics were performed to localize M1-, MOX-, and Mhem-like macrophages in the decidual basalis. RESULTS: Macrophages displayed diverse phenotypes in the decidua basalis with acute atherosis. M2-like macrophages were the most abundant subset in the decidua; yet, this macrophage subset did not change with the presence of acute atherosis. Decidual M1-like macrophages were increased in acute atherosis, and such macrophages displayed a pro-inflammatory phenotype, as indicated by the expression of iNOS and IL-12. Decidual M1-like pro-inflammatory macrophages were localized near both transformed and non-transformed vessels in the decidua basalis with acute atherosis. MOX and Mhem macrophages were also identified near transformed vessels in the decidua basalis with acute atherosis. Finally, monocyte-like cells were present on the vessel wall of non-transformed decidual vessels, indicating a possible intravascular source for macrophages in acute atherosis. CONCLUSION: Decidual macrophages display different phenotypes, namely M1-like, M2-like, MOX, and Mhem subsets. Yet, pro-inflammatory macrophages are enriched in the decidua basalis with acute atherosis. These findings provide a molecular foundation for future mechanistic inquiries about the role of pro-inflammatory macrophages in the pathogenesis of acute atherosis.