Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes.
Science
; 363(6423)2019 01 11.
Article
em En
| MEDLINE
| ID: mdl-30630901
ABSTRACT
Cytopenias are an important clinical problem associated with inflammatory disease and infection. We show that specialized phagocytes that internalize red blood cells develop in Toll-like receptor 7 (TLR7)-driven inflammation. TLR7 signaling caused the development of inflammatory hemophagocytes (iHPCs), which resemble splenic red pulp macrophages but are a distinct population derived from Ly6Chi monocytes. iHPCs were responsible for anemia and thrombocytopenia in TLR7-overexpressing mice, which have a macrophage activation syndrome (MAS)-like disease. Interferon regulatory factor 5 (IRF5), associated with MAS, participated in TLR7-driven iHPC differentiation. We also found iHPCs during experimental malarial anemia, in which they required endosomal TLR and MyD88 signaling for differentiation. Our findings uncover a mechanism by which TLR7 and TLR9 specify monocyte fate and identify a specialized population of phagocytes responsible for anemia and thrombocytopenia associated with inflammation and infection.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fagócitos
/
Glicoproteínas de Membrana
/
Transdução de Sinais
/
Receptor Toll-Like 9
/
Receptor 7 Toll-Like
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Síndrome de Ativação Macrofágica
/
Anemia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos