標題: Suppressed humoral immunity is associated with dengue nonstructural protein NS1-elicited anti-death receptor antibody fractions in mice
作者: Tsai, Chung-Lin
Sun, Der-Shan
Su, Mei-Tzu
Lien, Te-Sheng
Chen, Yen-Hsu
Lin, Chun-Yu
Huang, Chung-Hao
King, Chwan-Chuen
Li, Chen-Ru
Chen, Tai-Hung
Chiu, Yu-Hsiang
Lu, Chun-Chi
Chang, Hsin-Hou
生醫工程研究所
Institute of Biomedical Engineering
公開日期: 14-四月-2020
摘要: Dengue virus (DENV) infections may cause life-threatening dengue hemorrhagic fever (DHF). Suppressed protective immunity was shown in these patients. Although several hypotheses have been formulated, the mechanism of DENV-induced immunosuppression remains unclear. Previously, we found that cross-reactive antibodies against tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 1 (death receptor 4 [DR4]) were elicited in DHF patients, and that anti-DR4 autoantibody fractions were elicited by nonstructural protein 1 (NS1) immunizations in experimental mice. In this study, we found that anti-DR4 antibodies could suppress B lymphocyte function in vitro and in vivo. Treatment with the anti-DR4 immunoglobulin (Ig) induced caspase-dependent cell death in immortalized B lymphocyte Raji cells in vitro. Anti-DR4 Igs elicited by NS1 and DR4 immunizations markedly suppressed mouse spleen transitional T2 B (IgM(+)IgD(+)), bone marrow pre-pro-B (B220(+)CD43(+)), pre-B (B220(+)CD43(-)), and mature B cell (B220(+)IgD(+)) subsets in mice. Furthermore, functional analysis revealed that the pre-elicitation of anti-NS1 and anti-DR4 Ig titers suppressed subsequently neutralizing antibody production by immunization with DENV envelop protein. Our data suggest that the elicitation of anti-DR4 titers through DENV NS1 immunization plays a suppressive role in humoral immunity in mice.
URI: http://dx.doi.org/10.1038/s41598-020-62958-0
http://hdl.handle.net/11536/155446
ISSN: 2045-2322
DOI: 10.1038/s41598-020-62958-0
期刊: SCIENTIFIC REPORTS
Volume: 10
Issue: 1
起始頁: 0
結束頁: 0
顯示於類別:期刊論文