Macrophage Polarization in Physiological and Pathological Pregnancy

Abstract

The immunology of pregnancy is complex and poorly defined. During the complex process of pregnancy, macrophages secrete many cytokines/chemokines and play pivotal roles in the maintenance of maternal-fetal tolerance. Here, we summarized the current knowledge of macrophage polarization and the mechanisms involved in physiological or pathological pregnancy processes, including miscarriage, preeclampsia, and preterm birth. Although current evidence provides a compelling argument that macrophages are important in pregnancy, our understanding of the roles and mechanisms of macrophages in pregnancy is still rudimentary. Since macrophages exhibit functional plasticity, they may be ideal targets for therapeutic manipulation during pathological pregnancy. Additional studies are needed to better define the functions and mechanisms of various macrophage subsets in both normal and pathological pregnancy.

Keywords: abortion; macrophage; maternal-fetal interface; polarization; preeclampsia; preterm birth.

Figure 1

The different stumili, surface markers, secreted cytokines, and biological functions between M1 and M2 macrophages were summarized. CCL, chemokine (C-C motif) ligand; cMaf, c-musculoaponeurotic fibrosarconna; CXCL, chemokine (C-X-C) ligand; FIZZ1, resistin-like α; HIF, hypoxia inducible factor; iNOS, inducible nitric oxide synthase; IFN-γ, interferon-gamma; IL, interleukin; IRF, interferon regulatory factor; JMJD, Jumonji doman-containing protein; KLF, Kruppel-like factor; NF-κB, nuclear factor κB; KLF, Kruppel-like factor; LPS, lipopolysaccharides; MHC, major histocompatibility complex; PPAR, peroxisome proliferator-activated receptors; STAT, signal transducer and activator of transcription; TLR, Toll-like receptor; TNF-α, tumor necrosis factor alpha; TGF-β, transforming growth factor beta; VEGF, vascular endothelial growth factor; Ym1, chitinase 3-like 3.

Figure 2

The different stumili, surface markers, secreted cytokines, and biological functions of the M2 macrophage subsets were summarized.

Figure 3

The common and different characteristics between macrophages and dendritic cells were depicted according to their surface markers, transcription factors, and biological functions. BATF3, basic leucine zipper ATF-like transcription; BDCA, blood dendritic cells Ags; CLEC9A, C-type lectin 9A; E2-2, basic helix-loop-helix transcription factor; ID-2, inhibitor of DNA binding 2; XCR1, chemokine XC receptor 1; ZBTB46, zinc finger and BTB domain containing 46; ZEB2, Zinc finger E box–binding homeobox 2. Adapted from Rogers et al. (138) with permission from the publisher of Springer Nature.

Figure 4

The similarities and differences between Hofbauer cells and maternal macrophages in the placenta were depicted according to the origin, resident tissue and related diseases. Adapted from Coyne et al. (139) with permission from the publisher of Springer Nature.