Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells

Abstract

Hofbauer cells (HBCs) are a population of macrophages found in high abundance within the stroma of the first-trimester human placenta. HBCs are the only fetal immune cell population within the stroma of healthy placenta. However, the functional properties of these cells are poorly described. Aligning with their predicted origin via primitive hematopoiesis, we find that HBCs are transcriptionally similar to yolk sac macrophages. Phenotypically, HBCs can be identified as HLA-DR−FOLR2+ macrophages. We identify a number of factors that HBCs secrete (including OPN and MMP-9) that could affect placental angiogenesis and remodeling. We determine that HBCs have the capacity to play a defensive role, where they are responsive to Toll-like receptor stimulation and are microbicidal. Finally, we also identify a population of placenta-associated maternal macrophages (PAMM1a) that adhere to the placental surface and express factors, such as fibronectin, that may aid in repair.

Macrophage Plasticity in Reproduction and Environmental Influences on Their Function

“…As placental macrophages are observed before the fetal circulation is established, it is suggested that they are derived from mesenchymal cells in the villous stroma from early stages of gestation ( 95 – 97 ). A recent study additionally concluded that first trimester placental macrophages were derived from primitive hematopoiesis as they are transcriptionally similar to yolk sac derived macrophages but not embryonic monocytes ( 98 ). Other studies have suggested that upon development of the fetal circulation, placental macrophages are recruited from fetal monocytes in later stages of pregnancy as transitional forms of monocytes and placental macrophages are observed ( 99 – 101 ).…”

Gatekeepers of the fetus: Characterization of placental macrophages

“…Lastly, Thomas et al (2020) determine whether HBCs can be stimulated by various ligands representing infectious agents including viruses and bacteria. Given that some pathogens, such as Zika virus (Zimmerman et al, 2018;Jurado et al, 2016), replicate in HBCs as a mechanism to reach the intraamniotic cavity, these studies are critical to further understand the role of HBCs in placental defenses.…”

“…The authors then go on to further characterize both PAMMs and HBCs. Thomas et al (2020) identified two PAMM subsets in the fetal placenta based on CCR9 and FOLR2 staining (see figure, panel B). They found that PAMM-2 represented decidual macrophages whereas PAMM-1 was a separate subtype that could be separated into both macrophage and monocyte subtypes based on cell marker, cell phenotype, and transcriptional analysis.…”

“…Despite their abundance in placental villi, many of the functional and phenotypic characteristics of HBCs remain poorly defined, due largely to difficulties in both segregating these cells and maintaining their viability in order to characterize their phenotype and function. In a recent study published in JEM, Thomas et al (2020) develop a novel approach to characterize placental HBCs and further apply this approach to profile placenta-associated maternal monocyte/macrophage (PAMM) immune cell subsets (Thomas et al, 2020). This work provides highly impactful insights into the unique properties of HBCs and PAMMs and innovative tools to profile the characteristics of these cells.…”

“…In the first trimester, chorionic villi are immature and are covered by a contiguous layer called the syncytiotrophoblast (dark pink, SYN). Thomas et al (2020) define the characteristics of both maternal-and fetal-derived macrophages, termed PAMMs and HBCs. PAMM-1 (dark blue and light blue) and PAMM-2 (green) cells are identified by their HLA-DR, FOLR2 surface expression.…”