Transcriptional modification of host cells harboring Toxoplasma gondii bradyzoites prevents IFN gamma-mediated cell death

Simona Seizova, Ushma Ruparel, Alexandra L. Garnham, Stefanie M. Bader, Alessandro D. Uboldi, Michael J. Coffey, Lachlan W. Whitehead, Kelly L. Rogers, Christopher J. Tonkin (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Toxoplasma gondii develops a latent infection in the muscle and central nervous system that acts as a reservoir for acute-stage reactivation in vulnerable patients. Little is understood about how parasites manipulate host cells during latent infection and the impact this has on survival. We show that bradyzoites impart a unique transcriptional signature on infected host cells. Many of these transcriptional changes rely on protein export and result in the suppression of type I interferon (IFN) and IFNγ signaling more so than in acute stages. Loss of the protein export component, MYR1, abrogates transcriptional remodeling and prevents suppression of IFN signaling. Among the exported proteins, the inhibitor of STAT1 transcription (IST) plays a key role in limiting IFNγ signaling in bradyzoites. Furthermore, bradyzoite protein export protects host cells from IFNγ-mediated cell death, even when export is restricted to latent stages. These findings highlight the functional importance of host manipulation in Toxoplasma's bradyzoite stages.

Original languageEnglish
Pages (from-to)232-247.e6
Number of pages16
JournalCell Host & Microbe
Volume30
Issue number2
Early online date17 Dec 2021
DOIs
Publication statusPublished - 9 Feb 2022

Keywords

  • Apicomplexa
  • Myc-regulation 1 (MYR1)
  • Toxoplasma gondii
  • bradyzoites
  • cell death
  • interferon
  • latent infection
  • pathogen effector proteins
  • protein export

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