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Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages.
Thromb Haemost. 2016 Mar; 115(3):646-56.TH

Abstract

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.

Authors+Show Affiliations

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableProf. Yee-Shin Lin, Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 701, Taiwan, Tel.: +886 6 2353535 ext. 5646, Fax: +886 6 2082705, E-mail: yslin1@mail.ncku.edu.tw.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26632672

Citation

Wan, Shu-Wen, et al. "Anti-dengue Virus Nonstructural Protein 1 Antibodies Contribute to Platelet Phagocytosis By Macrophages." Thrombosis and Haemostasis, vol. 115, no. 3, 2016, pp. 646-56.
Wan SW, Yang YW, Chu YT, et al. Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages. Thromb Haemost. 2016;115(3):646-56.
Wan, S. W., Yang, Y. W., Chu, Y. T., Lin, C. F., Chang, C. P., Yeh, T. M., Anderson, R., & Lin, Y. S. (2016). Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages. Thrombosis and Haemostasis, 115(3), 646-56. https://doi.org/10.1160/TH15-06-0498
Wan SW, et al. Anti-dengue Virus Nonstructural Protein 1 Antibodies Contribute to Platelet Phagocytosis By Macrophages. Thromb Haemost. 2016;115(3):646-56. PubMed PMID: 26632672.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages. AU - Wan,Shu-Wen, AU - Yang,Yi-Wen, AU - Chu,Ya-Ting, AU - Lin,Chiou-Feng, AU - Chang,Chih-Peng, AU - Yeh,Trai-Ming, AU - Anderson,Robert, AU - Lin,Yee-Shin, Y1 - 2015/12/03/ PY - 2015/06/18/received PY - 2015/10/30/accepted PY - 2015/12/4/entrez PY - 2015/12/4/pubmed PY - 2017/2/12/medline KW - Dengue virus KW - nonstructural protein 1 KW - platelet phagocytosis SP - 646 EP - 56 JF - Thrombosis and haemostasis JO - Thromb Haemost VL - 115 IS - 3 N2 - 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. SN - 2567-689X UR - https://www.unboundmedicine.com/medline/citation/26632672/Anti_dengue_virus_nonstructural_protein_1_antibodies_contribute_to_platelet_phagocytosis_by_macrophages_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1160/TH15-06-0498 DB - PRIME DP - Unbound Medicine ER -