Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes

作者：Holly M. Akilesh, Matthew B. Buechler, Jeffrey M. Duggan, William O. Hahn, Bharati Matta, Xizhang Sun, Griffin M. Gessay, Elizabeth Whalen, Mike J. Mason, Scott Presnell, Keith B. Elkon, Adam Lacy‐Hulbert, Betsy Barnes, Marion Pepper, Jessica A. Hamerman · 发表于：Science · 年份：2019 · DOI：10.1126/science.aao5213 · 被引用次数：113 · 研究领域：Autoimmune and Inflammatory Disorders Research、Immune Cell Function and Interaction、Inflammasome and immune disorders

Unmasking an agent of inflammatory anemia Infectious and autoimmune diseases are associated with anemia and thrombocytopenia. A severe form of inflammatory cytopenia called macrophage activation syndrome (MAS) may occur during rheumatological disorders and viral infections. Akilesh et al. show that monocyte recognition of self- or pathogen-derived nucleic acids via Toll-like receptors 7 and 9 (TLR7 and TLR9) drives MAS-like disease in mice. TLR7 or TLR9 signaling in monocytes causes these cells to differentiate into inflammatory hematophagocytes (iHPCs), which are similar to but distinct from red pulp macrophages. Preventing iHPC differentiation by depleting monocytes relieves MAS-like symptoms. When mice were subjected to a model of malarial anemia, MyD88- and endosomal TLR-dependent iHPC differentiation also occurred. Thus, iHPCs may play a role in both MAS-driven and malarial anemia, as well as thrombocytopenia. Science , this issue p. eaao5213