title: Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages.
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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, and Core Research Laboratories, Rhode Island Hospital, Providence, RI 02912, USA.
authors.forename: Yun M
authors.initials: YM
authors.lastname: Ling
authors.forename: Michael H
authors.initials: MH
authors.lastname: Shaw
authors.forename: Carol
authors.initials: C
authors.lastname: Ayala
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coppens
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Taylor
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.forename: George S
authors.initials: GS
authors.lastname: Yap
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism* / Q000469:parasitology / Q000648:ultrastructure; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008561:Membrane Fusion / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014122:Toxoplasma / Q000276:immunology / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism* / Q000469:parasitology / Q000648:ultrastructure
chemical_list: D020558:GTP Phosphohydrolases; D007371:Interferon-gamma; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C101131:Igtp protein, mouse