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- Title
Suppressed humoral immunity is associated with dengue nonstructural protein NS1-elicited anti-death receptor antibody fractions in mice.
- Authors
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
- 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.
- Subjects
HUMORAL immunity; VIRAL nonstructural proteins; DEATH receptors; DENGUE viruses; IMMUNOSUPPRESSION
- Publication
Scientific Reports, 2020, Vol 10, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-020-62958-0