Migratory activation of parasitized dendritic cells by the protozoan Toxoplasma gondii 14-3-3 protein

Cell Microbiol. 2016 Nov;18(11):1537-1550. doi: 10.1111/cmi.12595. Epub 2016 May 6.


The obligate intracellular parasite Toxoplasma gondii exploits cells of the immune system to disseminate. Upon infection, parasitized dendritic cells (DCs) and microglia exhibit a hypermigratory phenotype in vitro that has been associated with enhancing parasite dissemination in vivo in mice. One unresolved question is how parasites commandeer parasitized cells to achieve systemic dissemination by a 'Trojan-horse' mechanism. By chromatography and mass spectrometry analyses, we identified an orthologue of the 14-3-3 protein family, T. gondii 14-3-3 (Tg14-3-3), as mediator of DC hypermotility. We demonstrate that parasite-derived polypeptide fractions enriched for Tg14-3-3 or recombinant Tg14-3-3 are sufficient to induce the hypermotile phenotype when introduced by protein transfection into murine DCs, human DCs or microglia. Further, gene transfer of Tg14-3-3 by lentiviral transduction induced hypermotility in primary human DCs. In parasites expressing Tg14-3-3 in a ligand-regulatable fashion, overexpression of Tg14-3-3 was correlated with induction of hypermotility in parasitized DCs. Localization studies in infected DCs identified Tg14-3-3 within the parasitophorous vacuolar space and a rapid recruitment of host cell 14-3-3 to the parasitophorous vacuole membrane. The present work identifies a determinant role for Tg14-3-3 in the induction of the migratory activation of immune cells by T. gondii. Collectively, the findings reveal Tg14-3-3 as a novel target for an intracellular pathogen that acts by hijacking the host cell's migratory properties to disseminate.

MeSH terms

  • 14-3-3 Proteins / physiology*
  • Animals
  • Cell Movement
  • Cells, Cultured
  • Dendritic Cells / parasitology
  • Dendritic Cells / physiology*
  • Host-Parasite Interactions
  • Humans
  • Mice, Inbred C57BL
  • Protozoan Proteins / physiology*
  • Toxoplasma / physiology*
  • Vacuoles / metabolism
  • Vacuoles / parasitology


  • 14-3-3 Proteins
  • Protozoan Proteins