title: Natural mannosylation of HIV-1 gp120 imposes no immunoregulatory effects in primary human plasmacytoid dendritic cells.
abstract: Plasmacytoid dendritic cells (pDCs) play a vital role in activation of anti-HIV-1 immunity, and suppression of pDCs might mitigate immune responses against HIV-1. HIV-1 gp120 high-mannose has been attributed immunosuppressive roles in human myeloid DCs, but no receptors for high-mannose have so far been reported on human pDCs. Here we show that upon activation with HIV-1 or by a synthetic compound triggering the same receptor in human pDCs as single-stranded RNA, human pDCs upregulate the mannose receptor (MR, CD206). To examine the functional outcome of this upregulation, inactivated intact or viable HIV-1 particles with various degrees of mannosylation were cultured with pDCs. Activation of pDCs was determined by assaying secretion of IFN-alpha, viability, and upregulation of several pDC-activation markers: CD40, CD86, HLA-DR, CCR7, and PD-L1. The level of activation negatively correlated with degree of mannosylation, however, subsequent reduction in the original mannosylation level had no effect on the pDC phenotype. Furthermore, two of the infectious HIV-1 strains induced profound necrosis in pDCs, also in a mannose-independent manner. We therefore conclude that natural mannosylation of HIV-1 is not involved in HIV-1-mediated immune suppression of pDCs.
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark. Electronic address: jonasns@gmail.com.
authors.forename: Jonas Nørskov
authors.initials: JN
authors.lastname: Søndergaard
authors.affiliation: Virus Research and Development, Department of Virology, Statens Serum Institut, DK-2300 Copenhagen, Denmark.
authors.forename: Lasse
authors.initials: L
authors.lastname: Vinner
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark. Electronic address: sbp@bio.dtu.dk.
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
mesh_terms: D051940:B7-2 Antigen / Q000096:biosynthesis; D060890:B7-H1 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis*; D008358:Mannose / Q000276:immunology / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000096:biosynthesis*; D054400:Receptors, CCR7 / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D051199:Toll-Like Receptor 7 / Q000276:immunology; D015854:Up-Regulation
chemical_list: D051940:B7-2 Antigen; D060890:B7-H1 Antigen; C515370:CCR7 protein, human; C423236:CD274 protein, human; D019013:CD40 Antigens; D015699:HIV Envelope Protein gp120; D006684:HLA-DR Antigens; D016898:Interferon-alpha; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; C514793:gp120 protein, Human immunodeficiency virus 1; D008358:Mannose
keywords: HIV-1; High mannose; Immune regulation; Plasmacytoid dendritic cell