Journal
BLOOD
Volume 124, Issue 5, Pages 791-802Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-11-536003
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Funding
- National Institutes of Health, National Heart, Lung, and Blood Institute [HL-112311-02, HL087201, RFA-HL-12-008, HL80442, N01-HC 25195, 1R01AG028321]
- National Institute of Allergy and Infectious Diseases [P01 AI078894, AI083215]
- National Heart, Lung, and Blood Institute T32 grant [HL007224]
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Viral infections have been associated with reduced platelet counts, the biological significance of which has remained elusive. Here, we show that infection with encephalomyocarditis virus (EMCV) rapidly reduces platelet count, and this response is attributed to platelet Toll-like receptor 7 (TLR7). Platelet-TLR7 stimulation mediates formation of large platelet-neutrophil aggregates, both in mouse and human blood. Intriguingly, this process results in internalization of platelet CD41-fragments by neutrophils, as assessed biochemically and visualized by microscopy, with no influence on platelet prothrombotic properties. The mechanism includes TLR7-mediated platelet granule release, translocation of P-selectin to the cellsurface, and a consequent increase in platelet-neutrophil adhesion. Viral infection of platelet-depleted mice also led to increased mortality. Transfusion of wild-type, TLR7-expressing platelets into TLR7-deficient mice caused a drop in platelet count and increased survival post EMCV infection. Thus, this study identifies a new link between platelets and their response to single-stranded RNA viruses that involves activation of TLR7. Finally, platelet-TLR7 stimulation is independent of thrombosis and has implications to the host immune response and survival.
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