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DOI: 10.1160/th15-06-0498
Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages
Financial support: This work was supported by Grants NSC101–2321-B006–002, NSC102–2325-B-006–006 and MOST103–2325-B-006–010 from The Ministry of Science and Technology, Taiwan.Publication History
Received:
18 June 2015
Accepted after major revision:
30 October 2015
Publication Date:
20 March 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201603/lookinside/thumbnails/10-1160-th15-06-0498-1.jpg)
Summary
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.
† These authors contributed equally.
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