title: DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells.
abstract: Early interactions between lung dendritic cells (LDCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, are thought to be critical for mounting a protective anti-mycobacterial immune response and for determining the outcome of infection. However, these interactions are poorly understood, at least at the molecular level. Here we show that M. tuberculosis enters human monocyte-derived DCs after binding to the recently identified lectin DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). By contrast, complement receptor (CR)3 and mannose receptor (MR), which are the main M. tuberculosis receptors on macrophages (Mphis), appeared to play a minor role, if any, in mycobacterial binding to DCs. The mycobacteria-specific lipoglycan lipoarabinomannan (LAM) was identified as a key ligand of DC-SIGN. Freshly isolated human LDCs were found to express DC-SIGN, and M. tuberculosis-derived material was detected in CD14(-)HLA-DR(+)DC-SIGN(+) cells in lymph nodes (LNs) from patients with tuberculosis. Thus, as for human immunodeficiency virus (HIV), which is captured by the same receptor, DC-SIGN-mediated entry of M. tuberculosis in DCs in vivo is likely to influence bacterial persistence and host immunity.
authors.affiliation: INSERM EMI-0013 Institut Universitaire d'Hématologie, Assistance Publique-Hôpitaux de Paris, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Tailleux
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Herrmann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pivert
authors.forename: Mary
authors.initials: M
authors.lastname: Jackson
authors.forename: Ali
authors.initials: A
authors.lastname: Amara
authors.forename: Luc
authors.initials: L
authors.lastname: Legres
authors.forename: Donatus
authors.initials: D
authors.lastname: Dreher
authors.forename: Laurent P
authors.initials: LP
authors.lastname: Nicod
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Gluckman
authors.forename: Philippe H
authors.initials: PH
authors.lastname: Lagrange
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Olivier
authors.initials: O
authors.lastname: Neyrolles
mesh_terms: D015703:Antigens, CD; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013997:Time Factors; D014376:Tuberculosis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D000097802:CD83 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000097802:CD83 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C050016:lipoarabinomannan