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

Jake R Thomas, Anna Appios, Xiaohui Zhao, Roksana Dutkiewicz, Maria Donde, Colin Y C Lee, Praveena Naidu, Christopher Lee, Joana Cerveira, Bing Liu, Florent Ginhoux, Graham Burton, Russell S Hamilton, Ashley Moffett, Andrew Sharkey, Naomi McGovern

Journal: The Journal of experimental medicine 2021;218(1):e20200891

PMID: 33075123

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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.

Address: Department of Pathology, University of Cambridge, Cambridge, UK.; Centre for Trophoblast Research, Departments of Physiology and Neuroscience, University of Cambridge, Cambridge, UK.; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.; Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.; State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China.; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China.; Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China.; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore.; Department of Genetics, University of Cambridge, Cambridge, UK.

DOI: 10.1084/jem.20200891

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MeSH Terms: Adult, Female, Folate Receptor 2, HLA-DR Antigens, Humans, Macrophages, Matrix Metalloproteinase 9, Placenta, Pregnancy, Pregnancy Trimester, First