Abstract
Apicomplexan protozoan pathogens avoid destruction and establish a replicative niche within host cells by forming a nonfusogenic parasitophorous vacuole (PV). Here we present evidence for lysosome-mediated degradation of Toxoplasma gondii after invasion of macrophages activated in vivo. Pathogen elimination was dependent on the interferon gamma inducible-p47 GTPase, IGTP, required PI3K activity, and was preceded by PV membrane indentation, vesiculation, disruption, and, surprisingly, stripping of the parasite plasma membrane. Denuded parasites were enveloped in autophagosome-like vacuoles, which ultimately fused with lysosomes. These observations outline a series of mechanisms used by effector cells to redirect the fate of a classically nonfusogenic intracellular pathogen toward a path of immune elimination.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Autophagy / physiology*
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Cell Membrane / metabolism*
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Cell Membrane / parasitology
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Cell Membrane / ultrastructure
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GTP Phosphohydrolases / genetics
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GTP Phosphohydrolases / metabolism
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Humans
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Immunohistochemistry
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Interferon-gamma / immunology
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Lysosomes / metabolism
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Macrophages* / cytology
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Macrophages* / immunology
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Macrophages* / metabolism
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Macrophages* / parasitology
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Membrane Fusion / physiology
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Mice
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Mice, Inbred Strains
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Mice, Knockout
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Toxoplasma / immunology
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Toxoplasma / metabolism*
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Vacuoles / metabolism*
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Vacuoles / parasitology
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Vacuoles / ultrastructure
Substances
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Phosphoinositide-3 Kinase Inhibitors
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Interferon-gamma
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GTP Phosphohydrolases
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Igtp protein, mouse