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¹ INSERM EMI-0013 Institut Universitaire d'Hématologie, Assistance Publique-Hôpitaux de Paris
² Service de Microbiologie, Assistance Publique-Hôpitaux de Paris
³ INSERM ERM-0220, Institut Universitaire d'Hématologie,Hôpital Saint-Louis, 75010 Paris, France
⁴ Groupe Virus et Immunité, Institut Pasteur, 75015 Paris, France
⁵ Unité de Génétique Mycobactérienne, Institut Pasteur, 75015 Paris, France
⁶ Unité d'Immunologie Virale, Institut Pasteur, 75015 Paris, France
⁷ Division de Pneumologie, Hopital Universitaire de Genève, 1211 Geneva, Switzerland

Address correspondence to O. Neyrolles, Institut Pasteur, Unité de Génétique Mycobactérienne, 28 rue du Dr Roux, 75015 Paris, France. Phone: 33-1-45-68-88-40; Fax: 33-1-45-68-88-43; E-mail: neyrolle{at}pasteur.fr

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 (Ms), 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.

Key Words: Mycobacteria • tuberculosis • dendritic cell • DC-SIGN • lipoarabinomannan

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