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Flotillin and RacH modulate the intracellular immunity of Dictyostelium to Mycobacterium marinum infection

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Published in Cellular Microbiology. 2007, vol. 9, no. 11, p. 2716-33
Abstract Mycobacterium marinum, a close relative of Mycobacterium tuberculosis, provides a useful model to study the pathogenesis of tuberculosis in genetically tractable model organisms. Using the amoeba Dictyostelium discoideum as a host, we show that expression of the M. marinum protein MAG24-1 is crucial to interfere with phagosome maturation. We find that two host proteins - the flotillin homologue vacuolin and p80, a predicted copper transporter - accumulate at the vacuole during pathogen replication until it finally ruptures and the bacteria are released into the host cytosol. Flotillin-1 accumulation at the replication niche and its rupture were also observed in human peripheral blood monocytes. By infecting various Dictyostelium mutants, we show that the absence of one of the two Dictyostelium vacuolin isoforms renders the host more immune to M. marinum. Conversely, the absence of the small GTPase RacH renders the host more susceptible to M. marinum proliferation but inhibits its cell-to-cell spreading.
Keywords AnimalsCells, CulturedCytoskeletal Proteins/genetics/metabolism/physiologyDictyostelium/immunology/metabolism/microbiologyFlow CytometryFluorescent Antibody TechniqueHumansImmunity, InnateMembrane Proteins/genetics/metabolism/physiologyMonocytes/immunology/metabolism/microbiologyMonomeric GTP-Binding Proteins/genetics/metabolismMutationMycobacterium Infections, Nontuberculous/microbiologyMycobacterium marinum/growth & development/immunology/metabolismPromoter Regions, Genetic/geneticsProtozoan Proteins/genetics/metabolism/physiology
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PMID: 17587329
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HAGEDORN, Monica, SOLDATI, Thierry. Flotillin and RacH modulate the intracellular immunity of Dictyostelium to Mycobacterium marinum infection. In: Cellular Microbiology, 2007, vol. 9, n° 11, p. 2716-33. https://archive-ouverte.unige.ch/unige:18910

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Deposited on : 2012-03-20

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