DC-SIGN Is the Major <i>Mycobacterium tuberculosis</i> Receptor on Human Dendritic Cells

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  • Ludovic Tailleux
    1INSERM EMI-0013 Institut Universitaire d'Hématologie, Assistance Publique-Hôpitaux de Paris
  • Olivier Schwartz
    4Groupe Virus et Immunité, Institut Pasteur, 75015 Paris, France
  • Jean-Louis Herrmann
    2Service de Microbiologie, Assistance Publique-Hôpitaux de Paris
  • Elisabeth Pivert
    5Unité de Génétique Mycobactérienne, Institut Pasteur, 75015 Paris, France
  • Mary Jackson
    5Unité de Génétique Mycobactérienne, Institut Pasteur, 75015 Paris, France
  • Ali Amara
    6Unité d'Immunologie Virale, Institut Pasteur, 75015 Paris, France
  • Luc Legres
    3INSERM ERM-0220, Institut Universitaire d'Hématologie,Hôpital Saint-Louis, 75010 Paris, France
  • Donatus Dreher
    7Division de Pneumologie, Hopital Universitaire de Genève, 1211 Geneva, Switzerland
  • Laurent P. Nicod
    7Division de Pneumologie, Hopital Universitaire de Genève, 1211 Geneva, Switzerland
  • Jean Claude Gluckman
    1INSERM EMI-0013 Institut Universitaire d'Hématologie, Assistance Publique-Hôpitaux de Paris
  • Philippe H. Lagrange
    2Service de Microbiologie, Assistance Publique-Hôpitaux de Paris
  • Brigitte Gicquel
    5Unité de Génétique Mycobactérienne, Institut Pasteur, 75015 Paris, France
  • Olivier Neyrolles
    5Unité de Génétique Mycobactérienne, Institut Pasteur, 75015 Paris, France

Abstract

<jats:p>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 (Mϕs), 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.</jats:p>

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