Abstract
Mycobacterium tuberculosis invades immune phagocytes and reprograms their otherwise bactericidal phagosome maturation pathway to establish a replication niche. Recent reports indicate that uptake of mycobacteria depends on the scavenger receptors class B (CD36 and SR-B1). We have established Dictyostelium as an alternative host model for pathogenic Mycobacterium marinum, a close cousin of M. tuberculosis. Dictyostelium discoideum possesses three CD36 homologs, the Lysosomal Membrane glycoProteins A, B and C. We investigated the importance of the proteins during phagocytic uptake, killing and digestion. Our results suggest that the plasma membrane protein LmpB is specifically implicated in the uptake of mycobacteria. LmpA, on the other hand, is found on phagolysosomes. Interestingly, cells with reduced LmpA protein levels showed impairments in actin-dependent processes such as phagocytosis and phagosome maturation. Additionally, these cells were more susceptible towards infection with M. marinum. Altogether, our results indicate that LmpA is a host cell defense factor, which modulates the dynamics of the actin cytoskeleton.
Published Version
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