Le lipoarabinomannane : structure et fonctions d'un glycolipide impliqué dans la pathogénie tuberculeuse.

Abstract

La tuberculose est responsable de 3 millions de deces par an. Sa reemergence est favorisee par la pandemie du SIDA et l' apparition de souches resistantes a divers antituberculeux. La maladie est causee par Mycobacterium tuberculosis, une bacterie capable d' infecter le macrophage et d' y survivre. Les interactions hote-pathogene necessaires a l' infection requierent des molecules associees a la paroi mycobacterienne. Parmi elles, le lipoarabinomannane (LAM) constitue un important facteur de virulence implique dans l' attenuation de la reponse immune de l' hote ainsi que dans l' adherence et l' internalisation du bacille dans les macrophages. Par ailleurs, au cours de son trafic intracellulaire, le LAM interagit avec des molecules du CD1 qui le presentent alors aux lymphocytes T. La mise a jour de la structure de ce glycolipide et l' identification des enzymes impliquees dans sa biosynthese devraient permettre de comprendre sa participation dans la pathogenie et d' ouvrir des pistes therapeutiques nouvelles.

Tuberculosis is the predominant cause of morbidity and mortality worldwide, infecting 8 million and killing 3 million people annually. The current situation is exacerbated by the HIV pandemic and the increased prevalence of multiple resistant strains of M. tuberculosis, while vaccine prophylaxis using BCG is unsatisfactory in many parts of the world. Mycobacteria have evolved many specific adaptations that enable them to infect and survive within host cells. Such host-pathogen interactions are mediated by specialized molecules, in particular those associated with the unique cellular envelope. Lipoarabinomannan (LAM) is regarded as the "lipopolysaccharide of mycobacteria" and is an important virulence factor. Its terminal mannose caps may be involved not only in attenuating the host immune response, but also in mediating the binding of mycobacteria to, and subsequent entry into macrophages.This may be further linked to an intracellular trafficking pathway through which LAM is presented by CD1 to T-cell subsets. More systematic genome type investigations of LAM biogenesis may reveal the true significance of this macromolecule in the immunopathogenesis of tuberculosis. As a consequence, the identification of new drug targets will permit the development of novel therapies against tuberculosis and other mycobacterial-related infections which may now be visualized through the advent of the recently sequenced M. tuberculosis genome.