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

Holly M. Akilesh | Zendy; Matthew B. Buechler | Zendy; Jeffrey M. Duggan | Zendy; William O. Hahn | Zendy; Bharati Matta | Zendy; Xizhang Sun | Zendy; Griffin M. Gessay | Zendy; Elizabeth Whalen | Zendy; Mike J. Mason | Zendy; Scott Presnell | Zendy; Keith B. Elkon | Zendy; Adam LacyHulbert | Zendy; Betsy Barnes | Zendy; Marion Pepper | Zendy; Jessica A. Hamerman | Zendy

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

Author(s) -

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 LacyHulbert,

Betsy Barnes,

Marion Pepper,

Jessica A. Hamerman

Publication year - 2019

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aao5213

Subject(s) - tlr7 , tlr9 , immunology , cytopenia , anemia , inflammation , macrophage activation syndrome , toll like receptor , receptor , medicine , biology , innate immune system , bone marrow , immune system , gene , genetics , gene expression , dna methylation , arthritis

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. Akileshet 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

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