Maturation of the Legionella pneumophila-containing phagosome into a phagolysosome within gamma interferon-activated macrophages.
Legionella pneumophila is an intracellular pathogen that modulates the biogenesis of its phagosome to evade endocytic vesicle traffic. The Legionella-containing phagosome (LCP) does not acquire any endocytic markers and is remodeled by the endoplasmic reticulum during early stages. Here we show that intracellular replication of L. pneumophila is inhibited in gamma interferon (IFN-gamma)-activated, bone marrow-derived mouse macrophages and IFN-gamma-activated, human monocyte-derived macrophages in a dose-dependent manner. This inhibition of intracellular replication is associated with the maturation of the LCP into a phagolysosome, as documented by the acquisition of LAMP-2, cathepsin D, and lysosomal tracer Texas Red ovalbumin, and with the failure of the LCP to be remodeled by the rough endoplasmic reticulum. We conclude that IFN-gamma-activated macrophages override the ability of L. pneumophila to evade endocytic fusion and that the LCP is processed through the "default" endosomal-lysosomal degradation pathway.
Santic
Marina
M
Department of Microbiology and Immunology, Room 316, University of Louisville College of Medicine, 319 Abraham Flexner Way 55A, Louisville, KY 40202, USA.
Molmeret
Maëlle
M
Abu Kwaik
Yousef
Y
D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000382:microbiology / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016952:Legionella pneumophila / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D008247:Lysosomes / Q000382:microbiology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000382:microbiology / Q000502:physiology; D010588:Phagosomes / Q000382:microbiology* / Q000502:physiology
D007371:Interferon-gamma