Intracellular Survival of Depends on Uptake and Degradation of Extracellular Matrix Glycosaminoglycans by Macrophages

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Macrophages are the primary host cells for a number of important microbial pathogens, including protozoan parasites belonging to the genus Leishmania. With few exceptions, little is known about the nutrient composition of the vacuolar compartments occupied by these pathogens. Leishmania proliferate within the mature phagolysosome compartment of macrophages and recent studies have suggested that intracellular parasite stages are dependent on the uptake of amino sugars. However, how Leishmania gain access to these sugars is unclear. In this study we have generated a Leishmania major mutant that is a strict auxotroph for the amino sugar, N-acetylglucosamine (GlcNAc). This mutant exhibited a similar virulence phenotype as wild type parasites in infected mice, but was unable to survive in cultured macrophages. The intracellular survival of the GlcNAc-auxotroph in cultured macrophages was restored by supplementation of the medium with the high molecular weight glycosaminoglycan, hyaluronan, which is rich in GlcNAc. Hyaluronan is a major component of vertebrate extracellular matrix and we show that it is rapidly degraded in Leishmania-induced skin lesions. Hyaluronan is internalized by infected macrophages and traffics to the Leishmania containing phagolysosome. Leishmania thus appear to exploit the critical role of macrophages in extracellular matrix turnover to obtain essential sugar carbon sources for growth and virulence.

Vyšlo v časopise: Intracellular Survival of Depends on Uptake and Degradation of Extracellular Matrix Glycosaminoglycans by Macrophages. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005136
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005136

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