title: Pseudo-Mannosylated DC-SIGN Ligands as Immunomodulants.
abstract: DC-SIGN, a C-type lectin mainly expressed by DCs, mediates antigen uptake and can induce specific immune responses, depending on the ligand involved. Owing to these properties, DC-SIGN is an attracting target for approaches aimed at tailoring the immune response towards specific immunologic outcomes. A multivalent DC-SIGN ligand (Polyman26), containing at its core a fluorescent "rod-like" spacer and able to inhibit DC-SIGN mediated HIV infection in nanomolar concentration, has been recently developed by our group. We investigated the internalization pattern and the ability of Polyman26 to elicit innate immune responses. Results obtained by confocal microscopy indicate that Polyman26 is internalized by DCs via receptor- mediated endocytosis and is then routed to endolysosomal compartments, thus being presented together with MHC class II molecules, with important implications for the development of vaccines. Moreover, Polyman26 up-regulated the production of β-chemokines and pro-inflammatory cytokines (including IL-1β, IL-6, IL-12, and TNFα) as well as the expression of TLR9 and CD40L. These results indicate that glycomimetic DC-SIGN ligands should be further investigated and suggest that these compounds could be used to differentially stimulate immune responses.
authors.affiliation: Chair of Immunology, Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Via G.B. Grassi 74, 20157 Milan, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Berzi
authors.affiliation: Department of Chemistry, University of Milan, Via C. Golgi 19, 20133, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ordanini
authors.affiliation: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 9101 6500 HB, Nijmegen, The Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: Joosten
authors.affiliation: Chair of Immunology, Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Via G.B. Grassi 74, 20157 Milan, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Trabattoni
authors.affiliation: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 9101 6500 HB, Nijmegen, The Netherlands.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cambi
authors.affiliation: Department of Chemistry, University of Milan, Via C. Golgi 19, 20133, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bernardi
authors.affiliation: Department of Pathophysiology and Transplantation, University of Milan, Via F.lli VCervi 93, 20090 Milan, Italy.|Don C. Gnocchi Foundation, IRCCS, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D018925:Chemokines / Q000378:metabolism; D003412:Cricetulus; D003713:Dendritic Cells / Q000166:cytology; D011992:Endosomes / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism; D006801:Humans; D007107:Immune System; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000737:chemistry; D015850:Interleukin-6 / Q000378:metabolism; D037102:Lectins / Q000737:chemistry*; D037181:Lectins, C-Type / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008247:Lysosomes / Q000378:metabolism; D008358:Mannose / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry*; D019707:Receptors, Chemokine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000941:Antigens; D015815:Cell Adhesion Molecules; D018925:Chemokines; D018664:Interleukin-12; D053583:Interleukin-1beta; D015850:Interleukin-6; D037102:Lectins; D037181:Lectins, C-Type; D008024:Ligands; D008358:Mannose; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin