Ligand-induced IFNGR1 down-regulation calibrates myeloid cell IFNγ responsiveness.
Life Sci Alliance
; 2(5)2019 10.
Article
de En
| MEDLINE
| ID: mdl-31585982
ABSTRACT
The type II IFN (IFNγ) enhances antimicrobial activity yet also drives expression of genes that amplify inflammatory responses. Hence, excessive IFNγ stimulation can be pathogenic. Here, we describe a previously unappreciated mechanism whereby IFNγ itself dampens myeloid cell activation. Staining of monocytes from Listeria monocytogenes-infected mice provided evidence of type I IFN-independent reductions in IFNGR1. IFNγ was subsequently found to reduce surface IFNGR1 on cultured murine myeloid cells and human CD14+ peripheral blood mononuclear cells. IFNγ-driven reductions in IFNGR1 were not explained by ligand-induced receptor internalization. Rather, IFNγ reduced macrophage Ifngr1 transcription by altering chromatin structure at putative Ifngr1 enhancer sites. This is a distinct mechanism from that used by type I IFNs. Ligand-induced reductions in IFNGR1 altered myeloid cell sensitivity to IFNγ, blunting activation of STAT1 and 3. Our data, thus, reveal a mechanism by which IFNGR1 abundance and myeloid cell sensitivity to IFNγ can be modulated in the absence of type I IFNs. Multiple mechanisms, thus, exist to calibrate macrophage IFNGR1 abundance, likely permitting the fine tuning of macrophage activation and inflammation.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Agranulocytes
/
Interféron gamma
/
Récepteur interféron
/
Cellules myéloïdes
/
Listeria monocytogenes
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Life Sci Alliance
Année:
2019
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique