Mannosylated lipoarabinomannan interacts with phagocytes.
Infection by Mycobacterium tuberculosis first involves its adhesion to mononuclear host phagocytes. Various macrophage opsonic and non-opsonic receptors are known to mediate this adhesion, with some specificity of mannosyl receptors for the more virulent strains. Mannosylated lipoarabinomannan, a major component of cell walls from M. tuberculosis and Mycobacterium bovis BCG, is endowed with mannooligosaccharide units that could mediate its binding to these latter receptors. To explore its interaction with murine immune cells by flow cytometry, we report a new procedure to fluorescently tag the polysaccharide molecules. We covalently labeled mannosylated lipoarabinomannan from M. bovis BCG with biotin, allowing formation of stable complexes with streptavidin coupled to a fluorochrome. In this work, we demonstrated that this major carbohydrate antigen interacts selectively with murine phagocytes, i.e. granulocytes and macrophages. This binding was affected by temperature and was serum- and divalent-cation-dependent. It also appears to involve a metabolically recycling protein receptor on the phagocyte surface and mannosyl aggretopes on the mannosylated lipoarabinomannan molecule. Thus, the latter may provide a means for mycobacteria to bind to and invade their host phagocytes. This molecule could constitute one of the early factors of mycobacterial virulence.
Venisse
A
A
Département des Glycoconjugués et Biomembranes, Laboratoire de Pharmacologie et Toxicologie Fondamentales du CNRS, Toulouse, France.
Fournié
J J
JJ
Puzo
G
G
D000818:Animals; D001667:Binding, Competitive; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D001798:Blood Proteins / Q000494:pharmacology; D002473:Cell Wall / Q000737:chemistry; D004705:Endocytosis; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008358:Mannose / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009163:Mycobacterium bovis / Q000737:chemistry*; D010586:Phagocytes / Q000378:metabolism*; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D013696:Temperature
D001798:Blood Proteins; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; C050016:lipoarabinomannan; D001710:Biotin; D008358:Mannose