Details

Autor(en) / Beteiligte

• Wan, Shu-Wen
• Yang, Yi-Wen
• Chu, Ya-Ting
• Lin, Chiou-Feng
• Chang, Chih-Peng
• Yeh, Trai-Ming
• Anderson, Robert
• Lin, Yee-Shin

Titel

Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages

Ist Teil von

• Thrombosis and haemostasis, 2016-03, Vol.115 (3), p.646

Ort / Verlag

Germany

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Thrombocytopenia is an important clinical manifestation of dengue disease. The hypotheses concerning the pathogenesis of thrombocytopenia include decreased production and increased destruction or consumption of platelets. We previously suggested a mechanism of molecular mimicry in which antibodies (Abs) directed against dengue virus (DENV) nonstructural protein 1 (NS1) cross-react with platelets. Furthermore, several lines of evidence show activation of endothelial cells (ECs) and macrophages are related to dengue disease severity. Previous studies also suggested that Ab-opsonised platelets facilitate the engulfment of platelets by macrophages. Here we show that TNF-α-activated ECs upregulate adhesion molecule expression to enhance the binding of platelets and macrophages and lead to anti-DENV NS1 Ab-mediated platelet phagocytosis. We further demonstrate that the interaction between macrophages and TNF-α-activated ECs requires binding of FcγR with the Fc region of platelet-bound anti-DENV NS1 Abs. Importantly, the binding of anti-DENV NS1 Abs to platelets did not interfere with platelet adhesion to ECs. The adhesion molecules ICAM-1 and β3 integrin expressed on ECs as well as the FcγR expressed on macrophages were critical in anti-DENV NS1 Ab-mediated platelet phagocytosis on activated ECs. Moreover, anti-DENV NS1 Abs dramatically enhanced platelet engulfment by macrophages in a murine model of DENV infection. Our study provides evidence for a novel role for anti-DENV NS1 Abs in the pathogenesis of thrombocytopenia in dengue disease by enhancing platelet phagocytosis by macrophages.