Scientific article
Open access

ATF6beta is a host cellular target of the Toxoplasma gondii virulence factor ROP18

Published inThe Journal of experimental medicine, vol. 208, no. 7, p. 1533-1546
Publication date2011

The ROP18 kinase has been identified as a key virulence determinant conferring a high mortality phenotype characteristic of type I Toxoplasma gondii strains. This major effector molecule is secreted by the rhoptries into the host cells during invasion; however, the molecular mechanisms by which this kinase exerts its pathogenic action remain poorly understood. In this study, we show that ROP18 targets the host endoplasmic reticulum-bound transcription factor ATF6β. Disruption of the ROP18 gene severely impairs acute toxoplasmosis by the type I RH strain. Because another virulence factor ROP16 kinase modulates immune responses through its N-terminal portion, we focus on the role of the N terminus of ROP18 in the subversion of host cellular functions. The N-terminal extension of ROP18 contributes to ATF6β-dependent pathogenicity by interacting with ATF6β and destabilizing it. The kinase activity of ROP18 is essential for proteasome-dependent degradation of ATF6β and for parasite virulence. Consistent with a key role for ATF6β in resistance against this intracellular pathogen, ATF6β-deficient mice exhibit a high susceptibility to infection by ROP18-deficient parasites. The results reveal that interference with ATF6β-dependent immune responses is a novel pathogenic mechanism induced by ROP18.

  • Activating Transcription Factor 6/deficiency/genetics/immunology/metabolism
  • Animals
  • Animals, Genetically Modified
  • Gene Knockout Techniques
  • Genes, Protozoan
  • Host-Parasite Interactions/immunology/physiology
  • Hypersensitivity, Immediate/etiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred ICR
  • Mice, Knockout
  • Protein-Serine-Threonine Kinases/genetics/toxicity
  • Toxoplasma/enzymology/genetics/pathogenicity
  • Toxoplasmosis, Animal/etiology/immunology
  • Virulence/physiology
  • Virulence Factors/genetics/toxicity
Citation (ISO format)
YAMAMOTO, Masahiro et al. ATF6beta is a host cellular target of the Toxoplasma gondii virulence factor ROP18. In: The Journal of experimental medicine, 2011, vol. 208, n° 7, p. 1533–1546. doi: 10.1084/jem.20101660
Main files (2)
Article (Accepted version)
Article (Accepted version)
ISSN of the journal0022-1007

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