Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it

Sebastian Virreira Winter, Wendy Niedelman, Kirk D. Jensen, Emily E. Rosowski, Lindsay Julien, Eric Spooner, Kacey Caradonna, Barbara A. Burleigh, Jeroen Saeij, Hidde L. Ploegh, Eva Maria Frickel

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere24434
JournalPLoS One
Volume6
Issue number9
DOIs
StatePublished - Sep 8 2011
Externally publishedYes

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Toxoplasma
Toxoplasma gondii
Vacuoles
vacuoles
binding proteins
Carrier Proteins
Virulence
virulence
mice
Parasites
Virulence Factors
Phagosomes
Trypanosoma cruzi
Toxoplasmosis
Animals
Immunoprecipitation
phagosomes
parasites
Cytokines
cytokines

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Virreira Winter, S., Niedelman, W., Jensen, K. D., Rosowski, E. E., Julien, L., Spooner, E., ... Frickel, E. M. (2011). Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it. PLoS One, 6(9), [e24434]. https://doi.org/10.1371/journal.pone.0024434

Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it. / Virreira Winter, Sebastian; Niedelman, Wendy; Jensen, Kirk D.; Rosowski, Emily E.; Julien, Lindsay; Spooner, Eric; Caradonna, Kacey; Burleigh, Barbara A.; Saeij, Jeroen; Ploegh, Hidde L.; Frickel, Eva Maria.

In: PLoS One, Vol. 6, No. 9, e24434, 08.09.2011.

Research output: Contribution to journalArticle

Virreira Winter, S, Niedelman, W, Jensen, KD, Rosowski, EE, Julien, L, Spooner, E, Caradonna, K, Burleigh, BA, Saeij, J, Ploegh, HL & Frickel, EM 2011, 'Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it', PLoS One, vol. 6, no. 9, e24434. https://doi.org/10.1371/journal.pone.0024434
Virreira Winter S, Niedelman W, Jensen KD, Rosowski EE, Julien L, Spooner E et al. Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it. PLoS One. 2011 Sep 8;6(9). e24434. https://doi.org/10.1371/journal.pone.0024434
Virreira Winter, Sebastian ; Niedelman, Wendy ; Jensen, Kirk D. ; Rosowski, Emily E. ; Julien, Lindsay ; Spooner, Eric ; Caradonna, Kacey ; Burleigh, Barbara A. ; Saeij, Jeroen ; Ploegh, Hidde L. ; Frickel, Eva Maria. / Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it. In: PLoS One. 2011 ; Vol. 6, No. 9.
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