Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes
Publication Date
2019
Journal Title
Science
Abstract
© 2017 The Authors. 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 Ly6C hi 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.
Volume Number
363
Issue Number
6423
Document Type
Article
Status
Faculty
Facility
School of Medicine
Primary Department
Molecular Medicine
Additional Departments
General Pediatrics
PMID
DOI
10.1126/science.aao5213