Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis

Joshua B. Radke, Danielle Worth, David Hong, Sherri Huang, William Sullivan, Emma H. Wilson, Michael W. White

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host.

Original languageEnglish (US)
Article numbere1007035
JournalPLoS Pathogens
Volume14
Issue number5
DOIs
StatePublished - May 1 2018

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Toxoplasmosis
Cysts
Toxoplasma
Surface Antigens
Parasites
Antigens
Cytokinesis
Vacuoles
Infection
Life Cycle Stages
S Phase
Mitosis
Monocytes
Cell Cycle
Animal Models
Gene Expression
Brain
Proteins

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Radke, J. B., Worth, D., Hong, D., Huang, S., Sullivan, W., Wilson, E. H., & White, M. W. (2018). Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis. PLoS Pathogens, 14(5), [e1007035]. https://doi.org/10.1371/journal.ppat.1007035

Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis. / Radke, Joshua B.; Worth, Danielle; Hong, David; Huang, Sherri; Sullivan, William; Wilson, Emma H.; White, Michael W.

In: PLoS Pathogens, Vol. 14, No. 5, e1007035, 01.05.2018.

Research output: Contribution to journalArticle

Radke, JB, Worth, D, Hong, D, Huang, S, Sullivan, W, Wilson, EH & White, MW 2018, 'Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis', PLoS Pathogens, vol. 14, no. 5, e1007035. https://doi.org/10.1371/journal.ppat.1007035
Radke, Joshua B. ; Worth, Danielle ; Hong, David ; Huang, Sherri ; Sullivan, William ; Wilson, Emma H. ; White, Michael W. / Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis. In: PLoS Pathogens. 2018 ; Vol. 14, No. 5.
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