MANNOSYLATED LIPOARABINOMANNAN INTERACTS WITH PHAGOCYTES

Infection by Mycobacterium tuberculosis first involves its adhesion to mononuclear host phagocytes. Various macrophage opsonic and non-opson ic receptors are known to mediate this adhesion, with some specificity of mannosyl receptors for the more virulent strains. Mannosylated lip oarabinomannan, a major component of cell walls from M. tuberculosis a nd 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 wi th biotin, allowing formation of stable complexes with streptavidin co upled 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 temperat ure and was serum- and divalent-cation-dependent. It also appears to i nvolve a metabolically recycling protein receptor on the phagocyte sur face and mannosyl aggretopes on the mannosylated lipoarabinomannan mol ecule. Thus, the latter may provide a means for mycobacteria to bind t o and invade their host phagocytes. This molecule could constitute one of the early factors of mycobacterial virulence.