Dengue virus neutralization in cells expressing Fc gamma receptors. PLoS One 8: e65231

Activating Fc gamma receptors (FccRs) in hematopoietic cells serve to remove antibody-opsonized antigens, including dengue virus (DENV), from systemic circulation. While neutralizing antibody concentrations provide humoral immunity, cross-reactive or sub-neutralizing levels of antibody can result in antibody-dependent enhancement of DENV infection that increases overall viral burden. Recently, it has been suggested that the antibody levels needed for DENV neutralization differs when different FccR is engaged. If this is true, the threshold titer used to infer immunity should be influenced by FccR usage. Here, using cells that express both activating and inhibitory FccRs, we show that the type of FccR engaged during phagocytosis can influence the antibody concentration requirement for DENV neutralization. We demonstrate that phagocytosis through FccRI requires significantly less antibody for complete DENV neutralization compared to FccRIIA. Furthermore, when DENV is opsonized with sub-neutralizing levels of antibody, FccRI-mediated phagocytosis resulted in significantly reduced DENV titers compared to FccRIIA. However, while FccRI may remove antibody-opsonized DENV more efficiently, this receptor is only preferentially engaged by clustering when neutralizing, but not sub-neutralizing antibody concentrations, were used. Collectively, our study demonstrates that activating FccR usage may influence antibody titers needed for DENV neutralization