NK Cells Activated through Antibody-Dependent Cell Cytotoxicity and Armed with Degranulation/IFN-? Production Suppress Antibody-dependent Enhancement of Dengue Viral Infection.

ABSTRACT: Antibody (Ab)-dependent enhancement (ADE) is a hypothesized mechanism of increased disease severity during secondary dengue virus (DENV) infection. This study investigates Ab-dependent cell cytotoxicity (ADCC) in counteracting ADE. In our system, DENV and DENV-immune sera were added to peripheral blood mononuclear cells (PBMCs), and ADE and NK cell activation were simultaneously monitored. ADE was detected in monocytes and a concurrent activation of NK cells was observed. Activated NK cells expressed IFN-? and CD107a. IFN-? was detected at 24?hours (24?h) followed by a rapid decline; CD107a expression peaked at 48?h and persisted for >7 days. Optimal activation of NK cells required the presence of enhancement serum together with ADE-affected monocytes and soluble factors, suggesting the coexistence of the counteractive ADCC Abs, in the same ADE-serum, capable of strongly promoting NK cell activation. The function of NK cells against ADE was demonstrated using a depletion assay. NK cell-depleted PBMCs had increased ADE as compared to whole PBMCs. Conversely, adding activated NK cells back into the NK-depleted-PBMCs or to purified monocytes decreased ADE. Blocking IFN-? expression also increased ADE. The study suggests that under ADE conditions, NK cells can be activated by ADCC Abs and can control the magnitude of ADE.

SUBMITTER: Sun P 

PROVIDER: S-EPMC6358599 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature