Baby's First Macrophage: Temporal Regulation of Hofbauer Cell Phenotype Influences Ligand-Mediated Innate Immune Responses across Gestation.
J Immunol
; 204(9): 2380-2391, 2020 05 01.
Article
em En
| MEDLINE
| ID: mdl-32213562
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-λ1 is a key placental IFN that appeared less protective than IFN-α, 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-γ plus LPS stimulation. Collectively, we demonstrate sequential, evolving immunity as part of the natural history of HCs through gestation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Placenta
/
Imunidade Inata
/
Macrófagos
Limite:
Adolescent
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article