Kinetics of phosphatidylinositol-3-phosphate acquisition differ between IgG bead-containing phagosomes and Mycobacterium tuberculosis-containing phagosomes.
A key aspect of Mycobacterium tuberculosis pathogenesis is the ability of the bacteria to survive within the host macrophage. A phagosome containing an IgG-coated bead matures into a lysosomal compartment as evidenced by a decrease in pH and an increased acquisition of hydrolytic enzymes. In contrast, when M. tuberculosis is phagocytosed, the maturation of the bacteria-containing phagosome is arrested, and the bacterium resides within a vacuole that retains characteristics of early endosomal compartments. M. tuberculosis-containing phagosomes are delayed in the recruitment of the early endosome autoantigen EEA1. Acquisition of EEA1 is dependent on the presence of phosphatidylinositol-3-phosphate (PI-3-P) generated by the kinase Vps34. We tested the hypothesis that delayed recruitment of EEA1 was due to altered kinetics of PI-3-P accumulation at the phagosomal membrane. Biochemical analysis of the phosphatidylinositol phosphates on M. tuberculosis-containing phagosomes revealed that PI-3-P acquisition was markedly retarded and reduced in comparison to IgG bead-containing phagosomes. Given the role these lipids play in the regulation of phagosome maturation these findings have implications with respect to the mechanisms behind the arrest of phagosome maturation.
Purdy
Georgiana E
GE
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Owens
Róisín M
RM
Bennett
Linda
L
Russell
David G
DG
Butcher
Barbara A
BA
D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D008264:Macrophages; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D010587:Phagocytosis; D010588:Phagosomes / Q000276:immunology* / Q000382:microbiology* / Q000502:physiology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D007074:Immunoglobulin G; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; C055525:phosphatidylinositol 3-phosphate