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Immunity. 2014 Jun 19;40(6):924-35. doi: 10.1016/j.immuni.2014.05.006. Epub 2014 Jun 12.

The parasitophorous vacuole membrane of Toxoplasma gondii is targeted for disruption by ubiquitin-like conjugation systems of autophagy.

Author information

1
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
2
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Microbiology, University of Chicago, Chicago, IL 60637, USA.
4
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
5
Department of Genetics, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
6
Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
7
Department of Pathology, University of Chicago, Chicago, IL 60637, USA. Electronic address: shwang@bsd.uchicago.edu.
8
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: virgin@wustl.edu.

Abstract

Autophagy is a lysosomal degradation pathway that is important in cellular homeostasis. Prior work showed a key role for the autophagy related 5 (Atg5) in resistance to Toxoplasma gondii. Here we show that the cassette of autophagy proteins involved in the conjugation of microtubule-associated protein 1 light chain 3 (LC3) to phosphatidylethanolamine, including Atg7, Atg3, and the Atg12-Atg5-Atg16L1 complex play crucial roles in the control of T. gondii in vitro and in vivo. In contrast, pharmacologic modulation of the degradative autophagy pathway or genetic deletion of other essential autophagy genes had no substantial effects. Rather the conjugation system was required for targeting of LC3 and interferon-γ effectors onto the vacuolar membrane of T. gondii and its consequent disruption. These data suggest that the ubiquitin-like conjugation systems that reorganize intracellular membranes during canonical autophagy are necessary for proper targeting of immune effectors to the intracellular vacuole membranes utilized by pathogens.

PMID:
24931121
PMCID:
PMC4107903
DOI:
10.1016/j.immuni.2014.05.006
[Indexed for MEDLINE]
Free PMC Article

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