Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis

• Published in: Blood Vol. 124; no. 5; pp. 791 - 802
• Main Authors: Koupenova, Milka, Vitseva, Olga, MacKay, Christopher R., Beaulieu, Lea M., Benjamin, Emelia J., Mick, Eric, Kurt-Jones, Evelyn A., Ravid, Katya, Freedman, Jane E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31-07-2014; American Society of Hematology
• Subjects: Animals; Blood Platelets - immunology; Blood Platelets - metabolism; Cardiovirus Infections - blood; Cardiovirus Infections - immunology; Cell Degranulation - immunology; Encephalomyocarditis virus - immunology; Encephalomyocarditis virus - metabolism; Female; Humans; Lipopolysaccharide Receptors - immunology; Lipopolysaccharide Receptors - metabolism; Male; Membrane Glycoproteins - blood; Membrane Glycoproteins - immunology; Mice; Mice, Knockout; Neutrophils - immunology; Neutrophils - metabolism; Platelet Count; Platelets and Thrombopoiesis; Secretory Vesicles - immunology; Secretory Vesicles - metabolism; Thrombosis; Toll-Like Receptor 7 - blood; Toll-Like Receptor 7 - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-11-536003

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 cell surface, 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.
•Activation of platelet-TLR7 receptor mediates platelet-viral immune responses with no effect on thrombosis.•This is the first study to show that platelets are necessary for survival during viral infection.