Functional and phenotypic characteristics of classical (M1) and alternatively activated (M2) macrophages and their role during normal and pathological pregnancy

Abstract

Macrophages belong to the population of mononuclear phagocytes of the innate immune system and represent one of the main subclasses of leukocytes in decidua. Due to the high phenotypic plasticity, decidual macrophages perform various functions during pregnancy. The dominant subclass is M2 polarized macrophages featured by the immunosuppressive phenotype and involved in maintaining maternal immune tolerance to the semi-allogeneic fetus. In the early period of pregnancy, pro-angiogenic factors produced by macrophages are engaged in the remodeling of the uterine spiral arteries, ensuring the formation of adequate blood circulation in the uteroplacental zone. Under microbial infection activation of macrophages via Toll receptors occurs and their phenotypic switching to the M1 proinflammatory phenotype. Strict space-time control of the M1/M2 polarization in this zone is necessary for a successful pregnancy. Dysregulation can contribute to aberrant activation of macrophages and pregnancy pathologies, such as spontaneous abortions, premature birth, preeclampsia, fetal growth retardation and intrauterine infections. This review summarizes the current understanding of the biology of macrophages, its classification with special regard to phenotypic and functional characteristics of decidual macrophages in the uteroplacental zone during normal pregnancy and the potential involvement of abnormally activated macrophages in the pathology of pregnancy.