Baby's First Macrophage: Temporal Regulation of Hofbauer Cell Phenotype Influences Ligand-Mediated Innate Immune Responses across Gestation

• Type of Material: Article
• Authors: Dominika Swieboda, Emory University; Erica Johnson, Emory University; Jacob Beaver, Emory University; Lisa Haddad, Emory University; Elizabeth Ann L Enninga, Mayo Clinic, Rochester; Matthew Hathcock, Mayo Clinic; Sarah Cordes, Emory University; Valerie Jean, Emory University; Ivy Lane, Emory University; Ioanna Skountzou, Emory University; Rana Chakraborty, Emory University
• Language: English
• Date: 2020-05-01
• Publisher: AMER ASSOC IMMUNOLOGISTS
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by The American Association of Immunologists, Inc.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.4049/jimmunol.1901185
• Title of Journal or Parent Work: JOURNAL OF IMMUNOLOGY
• Volume: 204
• Issue: 9
• Start Page: 2380
• End Page: 2391
• Grant/Funding Information: Research reported in this publication was supported in part by the Pediatrics/Winship Flow Cytometry Core of Winship Cancer Institute of Emory University, Children’s Healthcare of Atlanta.
• Keywords: Science & Technology; Immunology; FETAL; PARTURITION; PREGNANCY; VIRAL-INFECTION; PRETERM; Life Sciences & Biomedicine; INFLAMMATION; SUPPRESSORS; EXPRESSION; ALTERNATIVE ACTIVATION; M-CSF

Abstract

The importance of fetal placental macrophages (Hofbauer cell [HCs]) is underscored by their appearance 18 d postconception and maintenance through term; however, how human HCs evolve during healthy pregnancy and how microenvironment and ontogeny impact phenotype and function remain unknown. In this study, we comprehensively classify human HCs ex vivo, interrogate phenotypic plasticity, and characterize antiviral immune responses through gestation. Activated HCs were abundant in early pregnancy and decreased by term; molecular signatures emphasize inflammatory phenotypes early in gestation. Frequency of HCs with regulatory phenotypes remained high through term. Furthermore, term HCs exhibited blunted responses to stimulation, indicating reduced plasticity. IFN-l1 is a key placental IFN that appeared less protective than IFN-a, suggesting a potential weakness in antiviral immunity. Ligand-specific responses were temporally regulated: we noted an absence of inflammatory mediators and reduced antiviral gene transcription following RIG-I activation at term despite all HCs producing inflammatory mediators following IFN-g plus LPS stimulation. Collectively, we demonstrate sequential, evolving immunity as part of the natural history of HCs through gestation.