Dengue Virus Neutralization In Cells Expressing Fc Gamma Receptors

Activating Fc gamma receptors (Fc gamma Rs) 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 Fc gamma R is engaged. If this is true, the threshold titer used to infer immunity should be influenced by Fc gamma R usage. Here, using cells that express both activating and inhibitory Fc gamma Rs, we show that the type of Fc gamma R engaged during phagocytosis can influence the antibody concentration requirement for DENV neutralization. We demonstrate that phagocytosis through Fc gamma RI requires significantly less antibody for complete DENV neutralization compared to Fc gamma RIIA. Furthermore, when DENV is opsonized with sub-neutralizing levels of antibody, Fc gamma RI-mediated phagocytosis resulted in significantly reduced DENV titers compared to Fc gamma RIIA. However, while Fc gamma RI 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 Fc gamma R usage may influence antibody titers needed for DENV neutralization.