Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes.
basic_science · Level V
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- Record sourced from PubMed, PMID 30630901.
- Also identified by DOI 10.1126/science.aao5213 and PMC identifier 6413693.
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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 Ly6C<sup>hi</sup> 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.
Medical subject headings
- Anemia
- Macrophage Activation Syndrome
- Membrane Glycoproteins
- Phagocytes
- Signal Transduction
- Toll-Like Receptor 7
- Toll-Like Receptor 9