Flotillin and RacH modulate the intracellular immunity of Dictyostelium to Mycobacterium marinum infection.
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.
Hagedorn
Monica
M
Départment de Biochimie, Faculté des Sciences, Université de Genève, Sciences II, 30 quai Ernest Ansermet, CH-1211-Genève-4, Switzerland.
Soldati
Thierry
T
D000818:Animals; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004023:Dictyostelium / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009165:Mycobacterium Infections, Nontuberculous / Q000382:microbiology; D019910:Mycobacterium marinum / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D015800:Protozoan Proteins; C106354:flotillins; C105803:vac A protein, Dictyostelium discoideum; D020559:Monomeric GTP-Binding Proteins