title: M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells.
abstract: M. tuberculosis and M. leprae are considered to be prototypical intracellular pathogens that have evolved strategies to enable growth in the intracellular phagosomes. In contrast, we show that lysosomes rapidly fuse with the virulent M. tuberculosis- and M. leprae-containing phagosomes of human monocyte-derived dendritic cells and macrophages. After 2 days, M. tuberculosis progressively translocates from phagolysosomes into the cytosol in nonapoptotic cells. Cytosolic entry is also observed for M. leprae but not for vaccine strains such as M. bovis BCG or in heat-killed mycobacteria and is dependent upon secretion of the mycobacterial gene products CFP-10 and ESAT-6. The cytosolic bacterial localization and replication are pathogenic features of virulent mycobacteria, causing significant cell death within a week. This may also reveal a mechanism for MHC-based antigen presentation that is lacking in current vaccine strains.
authors.affiliation: The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: van der Wel
authors.forename: David
authors.initials: D
authors.lastname: Hava
authors.forename: Diane
authors.initials: D
authors.lastname: Houben
authors.forename: Donna
authors.initials: D
authors.lastname: Fluitsma
authors.forename: Maaike
authors.initials: M
authors.lastname: van Zon
authors.forename: Jason
authors.initials: J
authors.lastname: Pierson
authors.forename: Michael
authors.initials: M
authors.lastname: Brenner
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Peters
mesh_terms: D017951:Antigen Presentation / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002451:Cell Compartmentation / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003600:Cytosol / Q000502:physiology* / Q000648:ultrastructure; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006790:Host-Parasite Interactions / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000502:physiology / Q000648:ultrastructure; D008247:Lysosomes / Q000502:physiology* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009161:Mycobacterium / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D009166:Mycobacterium leprae / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D022423:Myeloid Cells / Q000382:microbiology* / Q000502:physiology / Q000648:ultrastructure; D010588:Phagosomes / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins