title: Neutralizing antibodies inhibit HIV-1 infection of plasmacytoid dendritic cells by an FcγRIIa independent mechanism and do not diminish cytokines production.
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.
authors.affiliation: 1] INSERM U1109, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France [2].
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lederle
authors.affiliation: INSERM U1109, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France.
authors.forename: Bin
authors.initials: B
authors.lastname: Su
authors.affiliation: 1] INSERM U1109, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France [2].
authors.forename: Vincent
authors.initials: V
authors.lastname: Holl
authors.affiliation: 1] INSERM U1109, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France [2].
authors.forename: Julien
authors.initials: J
authors.lastname: Penichon
authors.affiliation: INSERM U1109, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: INSERM U1109, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Decoville
authors.affiliation: INSERM U1109, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Laumond
authors.affiliation: INSERM U1109, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Moog
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000096:biosynthesis; D054407:Chemokine CCL4 / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D009500:Neutralization Tests; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014779:Virus Replication / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D054405:Chemokine CCL3; D054407:Chemokine CCL4; C080568:Fc gamma receptor IIA; D015483:HIV Antibodies; C508600:IL6 protein, human; D016898:Interferon-alpha; D015850:Interleukin-6; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha