Toxoplasma Gondii Bradyzoites Elicit Transcriptional Changes in Host Cells to Prevent IFNγ-Mediated Cell Death

Toxoplasma gondii bradyzoites are a chronic reservoir for disease reactivation in toxoplasmosis, which causes blindness and encephalitis. Acute-stage tachyzoites extensively manipulate their host cell by exporting a repertoire of proteins across the parasitophorous vacuolar membrane (PVM). This interferes with the hosts transcriptional program, allowing for persistence during immune attack. It is unknown how bradyzoites persist and what role host manipulation plays in latency. We show that bradyzoites drastically alter their hosts transcriptional program and this is dependent on the export of parasite proteins across the PVM-cyst wall. Furthermore, we demonstrate that protein export by bradyzoites is critical to protect infected host cells undergoing IFNγ stimulated cell death. Our work provides the first evidence the mechanisms used by latent Toxoplasma that allows for long-term survival and provides an interesting model to understand the differences in host manipulation used by pathogens during acute and chronic-stage infection.