Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes
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 (iHPC...
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Published in | Science (American Association for the Advancement of Science) Vol. 363; no. 6423 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
The American Association for the Advancement of Science
11.01.2019
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Subjects | |
Online Access | Get full text |
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Summary: | 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
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author Contributions: H.M.A, M.B.B and J.A.H. conceived and designed the study. H.M.A, M.B.B, J.M.D, W.O.H, X.S., G.G., B.M, and J.A.H performed experiments. S.P., E.W., M.M. performed RNA-Seq analysis. K.B.E, A.L-H., B.J.B and M.P. provided key reagents. H.M.A., M.B.B., W.O.H., K.B.E., A.L-H., M.P., B.J.B. and J.A.H wrote the manuscript. |
ISSN: | 0036-8075 1095-9203 |
DOI: | 10.1126/science.aao5213 |