Macrophage Plasticity in Reproduction and Environmental Influences on Their Function

Abstract

Macrophages are key components of the innate immune system and exhibit extensive plasticity and heterogeneity. They play a significant role in the non-pregnant cycling uterus and throughout gestation they contribute to various processes underpinning reproductive success including implantation, placentation and parturition. Macrophages are also present in breast milk and impart immunomodulatory benefits to the infant. For a healthy pregnancy, the maternal immune system must adapt to prevent fetal rejection and support development of the semi-allogenic fetus without compromising host defense. These functions are dependent on macrophage polarization which is governed by the local tissue microenvironmental milieu. Disruption of this microenvironment, possibly by environmental factors of infectious and non-infectious origin, can affect macrophage phenotype and function and is linked to adverse obstetric outcomes, e.g. spontaneous miscarriage and preterm birth. Determining environmental influences on cellular and molecular mechanisms that control macrophage polarization at the maternal-fetal interface and the role of this in pregnancy complications could support approaches to alleviating adverse pregnancy outcomes.

Fructose-1,6-bisphosphate prevents pregnancy loss by inducing decidual COX-2 + macrophage differentiation

“…Macrophage polarization has been reported to play an important role in normal pregnancy ( 13 , 22 ). Compared to COX-2 − dMφs, COX-2 + dMφs exhibited higher levels of CD163, CD206, CD209, and indolamine 2,3-dioxygenase 1 (IDO1) and lower levels of interferon-γ (IFN-γ), IL-23, and interferon regulatory factor 4 (IRF4) (fig.…”

“…During the different phases of gestation, macrophages undergo dynamic changes on the basis of environmental stimuli and mediators, differentiating to neither the classic M1 nor M2 subset ( 11 , 12 ). Accumulating evidence has indicated that M2 macrophages are the predominant phenotype in the decidua of early pregnancy ( 9 , 13 ). However, the molecular mechanisms underlying the activation and functions of dMφs are still largely unknown.…”

Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage

“…In general, decidual macrophages are characterized by an immunosuppressive phenotype as M2 polarization secreting IL-10, TGF-β, and G-CSF, supporting fetal-maternal immune tolerance during implantation ( 45 , 46 ). Abnormal macrophage polarization is related to many pregnancy complications, such as PE, premature birth, and RM ( 47 ). The previous study has shown that TGF-β can increase the invasiveness of placental cells in rats ( 48 ).…”

Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

“…The alternatively activated pathway, in the presence of Th2-derived cytokines such as IL-4, IL-10, IL-13, TGF-β, prostaglandin E2, or colony stimulating factor 1 (CSF1), gives rise to the M2-like macrophage phenotype, which typically facilitates tumor progression [ 143 , 144 ]. However, it is now understood that macrophage polarization extends beyond the dichotomy of M1/M2 phenotypes and is better defined as a spectrum [ 145 , 146 ]. Tumor-associated macrophages (TAMs) are considered to have an M1-like phenotype during the early process of tumorigenesis, and then eventually switch to an M2-like phenotype [ 147 ].…”