Neutralizing Antibodies Inhibit HIV-1 Infection of Plasmacytoid Dendritic Cells by an FcγRIIa Independent Mechanism and Do Not Diminish Cytokines Production

Plasmacytoid dendritic cells (pDC) expressing Fc gamma RIIa are antigen-presenting cells able to link innate and adaptive immunity and producing various cytokines and chemokines. Although highly restricted, they are able to replicate HIV-1. We determined the activity of anti-HIV-1 neutralizing antibodies (NAb) and non-neutralizing inhibitory antibodies (NNIAb) on the infection of primary pDC by HIV-1 primary isolates and analyzed cytokines and chemokines production. Neutralization assay was performed with primary pDC in the presence of serial antibodies (Ab) concentrations. In parallel, we measured the release of cytokines and chemokines by ELISA and CBA Flex assay. We found that NAb, but not NNIAb, inhibit HIV-1 replication in pDC. This inhibitory activity was lower than that detected for myeloid dendritic cells (mDC) infection and independent of Fc gamma RIIa expressed on pDC. Despite the complete protection, IFN-alpha production was detected in the supernatant of pDC treated with NAb VRC01, 4E10, PGT121, 10-1074, 10E8, or polyclonal IgG44 but not with NAb b12. Production of MIP-1 alpha, MIP-1 beta, IL-6, and TNF-alpha by pDC was also maintained in the presence of 4E10, b12 and VRC01. These findings suggest that pDC can be protected from HIV-1 infection by both NAb and IFN-alpha release triggered by the innate immune response during infection.