DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells.
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.
Tailleux
Ludovic
L
INSERM EMI-0013 Institut Universitaire d'Hématologie, Assistance Publique-Hôpitaux de Paris, France.
Schwartz
Olivier
O
Herrmann
Jean-Louis
JL
Pivert
Elisabeth
E
Jackson
Mary
M
Amara
Ali
A
Legres
Luc
L
Dreher
Donatus
D
Nicod
Laurent P
LP
Gluckman
Jean Claude
JC
Lagrange
Philippe H
PH
Gicquel
Brigitte
B
Neyrolles
Olivier
O
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
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