Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It
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Winter-2011-Determinants of GBP.pdf
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2.82 MB
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Author(s)
Caradonna, Kacey
Burleigh, Barbara A.
Winter, Sebastian Virreira
Niedelman, Wendy Leah
Rosowski, Emily Elizabeth
Julien, Lindsay
Spooner, Eric
Saeij, Jeroen
Ploegh, Hidde
Frickel, Eva-Maria
Date Issued
September 2011
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Virreira Winter, Sebastian et al. “Determinants of GBP Recruitment to Toxoplasma Gondii Vacuoles and the Parasitic Factors That Control It.” Ed. Silvia N. Moreno. PLoS ONE 6.9 (2011): e24434. Web. 15 Feb. 2012.
Version
Final published version
Abstract
IFN-γ is a major cytokine that mediates resistance against the intracellular parasite Toxoplasma gondii. The p65 guanylate-binding proteins (GBPs) are strongly induced by IFN-γ. We studied the behavior of murine GBP1 (mGBP1) upon infection with T. gondii in vitro and confirmed that IFN-γ-dependent re-localization of mGBP1 to the parasitophorous vacuole (PV) correlates with the virulence type of the parasite. We identified three parasitic factors, ROP16, ROP18, and GRA15 that determine strain-specific accumulation of mGBP1 on the PV. These highly polymorphic proteins are held responsible for a large part of the strain-specific differences in virulence. Therefore, our data suggest that virulence of T. gondii in animals may rely in part on recognition by GBPs. However, phagosomes or vacuoles containing Trypanosoma cruzi did not recruit mGBP1. Co-immunoprecipitation revealed mGBP2, mGBP4, and mGBP5 as binding partners of mGBP1. Indeed, mGBP2 and mGBP5 co-localize with mGBP1 in T. gondii-infected cells. T. gondii thus elicits a cell-autonomous immune response in mice with GBPs involved. Three parasitic virulence factors and unknown IFN-γ-dependent host factors regulate this complex process. Depending on the virulence of the strains involved, numerous GBPs are brought to the PV as part of a large, multimeric structure to combat T. gondii.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0024434
