Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2019

Latent Toxoplasma relies on effector proteins to prevent IFNg-mediated cell death (#23)

Christopher J. Tonkin 1 2 , Simona Seizova 1 2 , Alexandra Garnham 1 2 , Lachlan Whitehead 1 2 , Michael J. Coffey 1 2 , Kelly Rogers 1 2
  1. Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia
  2. Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia

Toxoplasma, the causative agent of toxoplasmosis, chronically infects up to a third of the world’s population and can lead to acute disease reactivation in the immunocompromised and cause progressive blindness in otherwise healthy individuals. Latent forms reside in the muscle and CNS where they are able to persist for life, and how this stage is able to avoid immune clearance and cause changes in the physiology of the brain is not known. We have recently begun investigating how Toxoplasma, in particular, latent bradyzoite forms manipulate their host cell. We show that bradyzoite-cysts drastically alter the host transcriptional program via effector protein export. We have identified the first effector protein in bradyzoite stages that accumulates in the host cell nucleus and blocks IFNg signalling.  Furthermore, we demonstrate protein export is critical for protecting bradyzoite infected host cells from undergoing IFNg-mediated programmed cell death, thus enabling persistence. This work provides the first evidence of the mechanisms used by Toxoplasma bradyzoites for their long-term survival and identifies host cell pathways manipulated by these latent forms.