Details

Autor(en) / Beteiligte

• Koupenova, Milka
• Vitseva, Olga
• MacKay, Christopher R.
• Beaulieu, Lea M.
• Benjamin, Emelia J.
• Mick, Eric
• Kurt-Jones, Evelyn A.
• Ravid, Katya
• Freedman, Jane E.

Titel

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

Ist Teil von

• Blood, 2014-07, Vol.124 (5), p.791-802

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.