Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 11, 2019
- Source ID
- 10.1126/science.aao5213
Entities
People
- Adam Lacy-Hulbert
- Betsy J Barnes
- Bharati Matta
- Elizabeth Whalen
- Griffin Gessay
- Holly M Akilesh
- Jeffrey M Duggan
- Jessica A Hamerman
- Keith B Elkon
- Marion Pepper
- Matthew B Buechler
- Mike J Mason
- Scott Presnell
- William O. Hahn
- Xizhang Sun
Organizations
- Alliance for Lupus Research
- American Association of Immunologists
- Benaroya Research Institute
- National Institutes of Health
- National Science Foundation
- The Feinstein Institute for Medical Research
- United States Department of Defense
- University of Washington