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

Author:

Thomas Jake R.12ORCID,Appios Anna12ORCID,Zhao Xiaohui2ORCID,Dutkiewicz Roksana1ORCID,Donde Maria1ORCID,Lee Colin Y.C.1ORCID,Naidu Praveena12ORCID,Lee Christopher34ORCID,Cerveira Joana1ORCID,Liu Bing567ORCID,Ginhoux Florent3489ORCID,Burton Graham2ORCID,Hamilton Russell S.210ORCID,Moffett Ashley12ORCID,Sharkey Andrew12ORCID,McGovern Naomi12ORCID

Affiliation:

1. Department of Pathology, University of Cambridge, Cambridge, UK

2. Centre for Trophoblast Research, Departments of Physiology and Neuroscience, University of Cambridge, Cambridge, UK

3. Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore

4. School of Biological Sciences, Nanyang Technological University, Singapore, Singapore

5. Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China

6. State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China

7. State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China

8. Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China

9. Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore

10. Department of Genetics, University of Cambridge, Cambridge, UK

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.

Funder

Wellcome Trust

Royal Society

Centre for Trophoblast Research

University of Cambridge

Medical Research Council

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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