| First Author | Akilesh HM | Year | 2019 |
| Journal | Science | Volume | 363 |
| Issue | 6423 | PubMed ID | 30630901 |
| Mgi Jnum | J:295155 | Mgi Id | MGI:6459697 |
| Doi | 10.1126/science.aao5213 | Citation | Akilesh HM, et al. (2019) Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes. Science 363(6423) |
| abstractText | 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. |
