Identification of Mycobacterial α-Glucan As a Novel Ligand for DC-SIGN: Involvement of Mycobacterial Capsular Polysaccharides in Host Immune Modulation - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2009

Identification of Mycobacterial α-Glucan As a Novel Ligand for DC-SIGN: Involvement of Mycobacterial Capsular Polysaccharides in Host Immune Modulation

Ryo Kakutani
  • Fonction : Auteur
Hiroki Takata
  • Fonction : Auteur

Résumé

Abstract Mycobacterium tuberculosis possesses a variety of immunomodulatory factors that influence the host immune response. When the bacillus encounters its target cell, the outermost components of its cell envelope are the first to interact. Mycobacteria, including M. tuberculosis, are surrounded by a loosely attached capsule that is mainly composed of proteins and polysaccharides. Although the chemical composition of the capsule is relatively well studied, its biological function is only poorly understood. The aim of this study was to further assess the functional role of the mycobacterial capsule by identifying host receptors that recognize its constituents. We focused on α-glucan, which is the dominant capsular polysaccharide. Here we demonstrate that M. tuberculosis α-glucan is a novel ligand for the C-type lectin DC-SIGN (dendritic cell-specific ICAM-3-grabbing nonintegrin). By using related glycogen structures, we show that recognition of α-glucans by DC-SIGN is a general feature and that the interaction is mediated by internal glucosyl residues. As for mannose-capped lipoarabinomannan, an abundant mycobacterial cell wall-associated glycolipid, binding of α-glucan to DC-SIGN stimulated the production of immunosuppressive IL-10 by LPS-activated monocyte-derived dendritic cells. By using specific inhibitors, we show that this IL-10 induction was DC-SIGN-dependent and also required acetylation of NF-κB. Finally, we demonstrate that purified M. tuberculosis α-glucan, in contrast to what has been reported for fungal α-glucan, was unable to activate TLR2.

Dates et versions

hal-04023554 , version 1 (10-03-2023)

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Jeroen Geurtsen, Sunita Chedammi, Joram Mesters, Marlène Cot, Nicole Driessen, et al.. Identification of Mycobacterial α-Glucan As a Novel Ligand for DC-SIGN: Involvement of Mycobacterial Capsular Polysaccharides in Host Immune Modulation. Journal of Immunology, 2009, 183 (8), pp.5221-5231. ⟨10.4049/jimmunol.0900768⟩. ⟨hal-04023554⟩
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