Elsevier

Pathologie Biologie

Volume 53, Issue 1, January 2005, Pages 35-40
Pathologie Biologie

Biological advance
Dendritic cells and Mycobacterium tuberculosis: which is the Trojan horse?Cellules dendritiques et Mycobacterium tuberculosis : Qui est le cheval de Troie ?

https://doi.org/10.1016/j.patbio.2004.01.004Get rights and content

Abstract

A new scenario has been unraveled recently—the interaction between the human dendritic cell (DC) and Mycobacterium tuberculosis. Whether this encounter represents a defense mechanism by the invaded host, or a smoke screen, masking the presence of an invader is still unknown. The intracellular behavior of M. tuberculosis inside DCs differs compared to macrophages (Mφs), with a failure of replication. The intracellular compartment of the DC, disconnected from the exocytic and endocytic pathways, and characterized by the absence of endoplasmic reticulum and Golgi features, places M. tuberculosis in a hostile environment, where a ready source of nutrients is scarce. The differential behavior inside Mφs and DCs is linked to a different portal of entry. DCs harbor surface lectins receptors, like DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN/CD209), a binding site which is absent on Mφs. This receptor interacts exclusively with M. tuberculosis. The ligand is the mannose-capped lipoarabinomanan (LAM), absent from atypical mycobacteria. M. smegmatis, M. chelonae and M. fortuitum, which possess LAM capped with phosphoinositides residues, do not bind to DC-SIGN, demonstrating a role for DC-SIGN as a ‘pattern-recognition receptor’ with the ability to differentiate between pathogenic and non-pathogenic mycobacteria. Interactions of M. tuberculosis with DC-SIGN have antiinflammatory effects. Whether this property is of benefit to the invader remains to be discovered.

Résumé

Un nouveau scénario a été récemment mis en évidence : l’interaction entre les cellules dendritiques humaines (DCs) et Mycobacterium tuberculosis. Que ce scénario représente un mécanisme de défense de l’hôte infecté ou un moyen simple pour l’agent pathogène de se cacher de l’hôte, reste encore inconnu. Le comportement intracellulaire de M. tuberculosis dans les DCs diffère de celui observé dans les macrophages humains (Mφs), avec une absence de multiplication intracellulaire. Le compartiment intracellulaire (ou phagosome) des DCs, séparé des voies d’endocytose et d’exocytose cellulaire et caractérisé par l’absence de marqueurs appartenant au réticulum endoplasmique et à l’appareil de Golgi, place M. tuberculosis au sein d’un environnement hostile, où les nutriments sont en faible quantité. Cette différence de comportement peut être liée à une différence de « porte d’entrée » de M. tuberculosis, entre Mφs et DCs. Les DCs présentent en effet un récepteur appelé DC-SIGN/CD209 (DC-specific intercellular adhesion molecule-3 grabbing nonintegrin) qui est absent de la surface des Mφs. Ce récepteur interagit spécifiquement avec M. tuberculosis. Son ligand est le lipoarabinomannane (LAM), spécifique de M. tuberculosis grâce à la présence de coiffes mannose à sa surface, absentes des autres mycobactéries. M. smegmatis, M. chelonae, M. fortuitum, qui possèdent un LAM coiffé de résidus phosphoinositides, ne se lient pas à DC-SIGN, démontrant un rôle spécifique de DC-DIGN comme pattern recognition receptor, grâce à sa propriété de différencier les mycobactéries pathogènes, des mycobactéries atypiques. Les interactions entre DCs et M. tuberculosis auraient des propriétés anti-inflammatoires. Que cette propriété soit bénéfique à l’envahisseur, ou à l’hôte infecté, reste à découvrir.

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