Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes-Reference-Cited by-同舟云学术

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

Published:2019-01-11 Issue:6423 Volume:363 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Akilesh Holly M.¹²^ORCID,Buechler Matthew B.¹³^ORCID,Duggan Jeffrey M.¹³^ORCID,Hahn William O.³⁴,Matta Bharati⁵^ORCID,Sun Xizhang²,Gessay Griffin¹^ORCID,Whalen Elizabeth⁶^ORCID,Mason Michael⁶^ORCID,Presnell Scott R.⁶^ORCID,Elkon Keith B.¹²^ORCID,Lacy-Hulbert Adam¹³^ORCID,Barnes Betsy J.⁵^ORCID,Pepper Marion³,Hamerman Jessica A.¹³^ORCID

Affiliation:

1. Immunology Program, Benaroya Research Institute, Seattle, WA, USA.

2. Division of Rheumatology, Department of Medicine, University of Washington, Seattle, WA, USA.

3. Department of Immunology, University of Washington, Seattle, WA, USA.

4. Division of Allergy and Infectious Disease, Department of Medicine, University of Washington, Seattle, WA, USA.

5. Center for Autoimmune, Musculoskeletal and Hematopoietic Disease, The Feinstein Institute for Medical Research, Manhasset, NY, USA.

6. Systems Immunology Program, Benaroya Research Institute, Seattle, WA, USA.

Abstract

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

Funder

National Science Foundation

National Institutes of Health

American Association of Immunologists

U.S. Department of Defense

Lupus Research Alliance

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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