@article{45e3140347054d56bb4fbc5f78af3b6e,
title = "Suppressed humoral immunity is associated with dengue nonstructural protein NS1-elicited anti-death receptor antibody fractions in mice",
abstract = "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.",
author = "Tsai, {Chung Lin} and Sun, {Der Shan} and Su, {Mei Tzu} and Lien, {Te Sheng} and Chen, {Yen Hsu} and Lin, {Chun Yu} and Huang, {Chung Hao} and King, {Chwan Chuen} and Li, {Chen Ru} and Chen, {Tai Hung} and Chiu, {Yu Hsiang} and Lu, {Chun Chi} and Chang, {Hsin Hou}",
note = "Funding Information: The authors want to thank Professor Michel Hahne, Department of Immunology and Oncology, Centro Nacional de Biotecnolog{\'i}a, Madrid, Spain, for his kindly provided TACI cDNA, by which we constructed the TACI expression plasmid. The authors also want to thank Experimental Animal Center, Tzu-Chi University, for the help on the animal care and experimental consultant. This work was supported by Ministry of Science and Technology, Taiwan (98-2320-B-320-004MY3, 101-2320-B-320-004-MY3, 105-2923-B-320-001-MY3, 107-2311-B-320-002 -MY3 to HHC), Tzu-Chi University (TCIRP95002; TCIRP98001; TCIRP101001 to HHC and DSS), and Tzu-Chi Medical Foundation (TCMMP104-06, TCMMP108-04; TCAS-108-01 and TC-NHRI105 to HHC and DSS). This work is supported by research funding from Ministry of Science and Technology, Taiwan (98-2320-B-320-004MY3, 101-2320-B-320-004-MY3, 105-2923-B-320-001-MY3, 107-2311-B-320-002 -MY3 to HHC), Tzu-Chi University (TCIRP95002; TCIRP98001; TCIRP101001 to HHC and DSS), and Tzu-Chi Medical Foundation (TCMMP104-06, TCMMP108-04; TCAS-108-01 and TC-NHRI105 to HHC and DSS). Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41598-020-62958-0",
language = "English",
volume = "10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}
