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

Abstract

Hofbauer cells (HBC) are a population of macrophages found in high abundance within the stroma of the first trimester human placenta. HBC 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 haematopoiesis, we find that HBC are transcriptionally similar to yolk sac macrophages. Phenotypically, HBC can be identified as HLA-DR-FOLR2+ macrophages. We identify a number of factors HBC secrete (including IL-8 and MMP-9) that could affect placental angiogenesis and remodelling. We determine that HBC 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.SummaryUsing transcriptomic and proteomic data, Thomas, J. et al, analyse human first trimester placental macrophages and delineate markers that identify them. They also reveal that Hofbauer cells have microbicidal capacity, providing the fetus with an additional layer of protection from certain microbes.One sentence summaryHofbauer cells are primitive placental macrophages with a unique phenotype and role in fetal defence.Non-standard abbreviationPlacental associated maternal monocytes/macrophages, PAMM.

Mild/Asymptomatic Maternal SARS-CoV-2 Infection Leads to Immune Paralysis in Fetal Circulation and Immune Dysregulation in Fetal-Placental Tissues

“…Dimensionality reduction was performed using RunPCA function to obtain the first 30 principal components and clusters visualized using Seurat's RunUMAP function. Cell types were assigned to individual clusters using FindAllMarkers function with a log2 fold change cutoff of at least 0.4, FDR<0.05, and using a known catalog of well-characterized scRNA markers for human PBMC and villous leukocytes (Supplemental Table 1) 42 . Differential gene expression analysis was performed using MAST function in Seurat.…”

“…Given the observed changes in circulating fetal immune cells and our recently described changes in decidual leukocytes with maternal SARS-CoV-2 infection 12 , we next interrogated the impact of maternal SARS-CoV-2 infection on the immune landscape of chorionic villi (fetal side of unique cell clusters that contained cells from both groups (Figure 5A and Supplemental Figure 2A). These clusters were annotated (Figure 5B and Supplemental Figure 2B) based on markers previously described for the first-trimester villous immune landscape 42 . HBCs were defined based on high levels of FOLR2 and low levels of HLA-DRA with a proliferating HBC cluster also expressing high levels of MKI67.…”

“…Therefore, perturbations in the maternal circulation and decidua tissues likely expand into fetal villous tissues and, thus, fetal circulation 94,95 . The fetus-derived chorionic villous is comprised exclusively of macrophages, a major population being Hofbauer cells (HBC) that secrete factors important for placental angiogenesis and remodeling but also offer protection from bacterial pathogens 42,96 . HBC also expand in numbers with adverse .…”

“…In addition to fetal HBC, the placental villi harbor additional maternal monocyte/macrophage subsets that assist in placental repair mechanisms and possibly the prevention of microbial transmission 42,96 . Among these, are PAMM1a cells (maternal macrophages), which did not vary in numbers with maternal infection but exhibited transcriptional signatures associated with cell activation, cell death, and vessel morphogenesis.…”

“…These observations suggest activation of the infiltrating maternal macrophages to repair possible placental structural damage caused by SARS-CoV-2. PAMM1b cells are less abundant in healthy villous tissues and are transcriptionally comparable to adult circulating classical monocytes 42 . In addition to their expansion with maternal SARS-CoV-2 infection, we observed a significant rewiring of their transcriptional states suggestive of enhanced activation and immune effector function.…”