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 γ 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.
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4 September 2006
Brief Definitive Report|
August 28 2006
Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages
Yun M. Ling,
Yun M. Ling
1Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912
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Michael H. Shaw,
Michael H. Shaw
1Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912
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Carol Ayala,
Carol Ayala
2Core Research Laboratories, Rhode Island Hospital, Providence, RI 02903
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Isabelle Coppens,
Isabelle Coppens
3Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Public Health, Baltimore, MD 21205
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Gregory A. Taylor,
Gregory A. Taylor
4Department of Medicine, Department of Molecular Genetics & Microbiology, Department of Immunology, and Center for the Study of Aging, Duke University and GRECC VA Medical Center, Durham, NC 27710
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David J.P. Ferguson,
David J.P. Ferguson
5Nuffield Department of Pathology, John Radcliffe Hospital, Oxford University, Oxford OX3 9DU, UK
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George S. Yap
George S. Yap
1Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912
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Yun M. Ling
1Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912
Michael H. Shaw
1Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912
Carol Ayala
2Core Research Laboratories, Rhode Island Hospital, Providence, RI 02903
Isabelle Coppens
3Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Public Health, Baltimore, MD 21205
Gregory A. Taylor
4Department of Medicine, Department of Molecular Genetics & Microbiology, Department of Immunology, and Center for the Study of Aging, Duke University and GRECC VA Medical Center, Durham, NC 27710
David J.P. Ferguson
5Nuffield Department of Pathology, John Radcliffe Hospital, Oxford University, Oxford OX3 9DU, UK
George S. Yap
1Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912
CORRESPONDENCE George S. Yap: [email protected]
Received:
June 21 2006
Accepted:
August 03 2006
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2006
J Exp Med (2006) 203 (9): 2063–2071.
Article history
Received:
June 21 2006
Accepted:
August 03 2006
Citation
Yun M. Ling, Michael H. Shaw, Carol Ayala, Isabelle Coppens, Gregory A. Taylor, David J.P. Ferguson, George S. Yap; Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages . J Exp Med 4 September 2006; 203 (9): 2063–2071. doi: https://doi.org/10.1084/jem.20061318
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