Trophoblast Induces Monocyte Differentiation Into CD14+/CD16+ Macrophages

Abstract

Problem During early pregnancy, macrophages and trophoblast come into close contact during placenta development, and regulated cross talk between these cellular compartments is crucial for maintaining a healthy pregnancy. As trophoblast cells constitutively secrete many chemokines and cytokines, we hypothesize that trophoblast secreted factors can differentiate monocytes into a decidual phenotype. In this study, we describe a unique macrophage phenotype following monocytes’ exposure to trophoblast soluble factors. Method of Study Peripheral blood monocytes were treated with or without conditioned media (CM) from first trimester trophoblast cells. Phenotypic changes and phagocytic capacity were determined by flow cytometry. Cytokine and chemokine production was determined by multiplex analysis. Results Monocytes exposed to trophoblast factors undergo morphologic changes characterized by a gain in size and complexity and acquire a unique phenotype characterized by gain of CD14 surface expression as well as CD16. The presence of CD14+/CD16+ macrophages was confirmed in normal decidua. These cells secrete higher levels of IL-1b, IL-10, and IP-10 and have increased capacity for phagocytosis. Conclusion We demonstrate that trophoblast secreted factors can induce monocyte differentiation into a unique macrophage phenotype. These findings suggest that the microenvironment of the placenta can modulate the phenotype of macrophages present at the decidua.

Hypoxia regulates placental angiogenesis via alternatively activated macrophages

“…22,41 It is interesting to note that exposure of macrophages to severe hypoxia for 48 hours abolished Hif1a mRNA expression (Figure 3). 6 Another limitation is that we did not include other cell types that might cross-talk with macrophages, such as trophoblast cells 44,45 and endothelial cells, as they may also regulate angiogenic function of macrophages. In our study, we treated M2 cells with different doses of progesterone and estradiol within the range found at the feto-maternal interface.…”

Human trophoblast cells induced MDSCs from peripheral blood CD14+ myelomonocytic cells via elevated levels of CCL2

“…As these cells encounter various maternal immune cells, particularly CD14 1 myelomonocytic cells, interactive cross-talk between the cellular compartments is critical for maternal-fetal tolerance [17][18][19]31 . Previous studies have shown that trophoblast cells express a wide range of chemokines and cytokines, which induce CD14 1 myelomonocytic cell differentiation into special subtypes with higher levels of IL10 and increased capacity for phagocytosis 31,32 . We have performed several functional analyses, revealing that HTR8/SVneo cell-induced CD14 1 HLA-DR 2/low cells effectively inhibited the expansion of CD3/ CD28-activated autologous CD4 1 T cells (Figure 2).…”

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