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Abstract
Plasmacytoid dendritic cells (pDC) expressing FcγRIIa 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 FcγRIIa expressed on pDC. Despite the complete protection, IFN-α 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-1α, MIP-1β, IL-6, and TNF-α 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-α release triggered by the innate immune response during infection.
Highlights
Alexandre Lederle{, Bin Su, Vincent Holl*, Julien Penichon{, Sylvie Schmidt, Thomas Decoville, Geraldine Laumond & Christiane Moog
In order to determine the involvement of FccRIIa in Ab-mediated inhibition, the inhibitory effect neutralizing antibodies (NAb) b12 and its mutant LALA that is unable to bind to FccRs12 was compared on human immunodeficiency virus (HIV)-1 replication in Plasmacytoid dendritic cells (pDC)
We demonstrated that NAb, but not neutralizing inhibitory antibodies (NNIAb), inhibited primary pDC infection by HIV-1
Summary
Alexandre Lederle{, Bin Su, Vincent Holl*, Julien Penichon{, Sylvie Schmidt, Thomas Decoville, Geraldine Laumond & Christiane Moog. Novel broadly NAb (e.g.VRC01, PGT family, 3BNC117, 10-1074, etc) capable of neutralizing a large spectrum of HIV-1 isolates of various clades have been discovered, in addition to the previously well characterized NAb b12, 2G12, 447-52D, 2F5, 4E104–11 These Ab efficiently inhibit HIV-1 primary isolates or pseudoviruses in vitro in conventional neutralization assay with PBMC or TZM-bl cells. PDC produce cytokines and in innate immune response (reviewed in27,28) and in the triggering of chemokines, and in particular large amounts of type I interferon the adaptive immune response by presenting antigens, with (IFN) in the presence of HIV26 These cells play an important role less efficiency than mDC (reviewed in[29,30]). Ab were tested together on pDC from two different healthy donors and data represent the means 6 SD of two independent experiments
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