Oral Presentation Lorne Infection and Immunity 2022

Mechanisms of Survival of Latent Toxoplasma (#6)

Chris Tonkin 1
  1. WEHI, Melbourne, VIC, Australia

Toxoplasma latently infects one in four humans, residing in the brain and muscle, and where it can reactive into acute infection in immunocompromised patients and can cause progressive blindness in otherwise heatlh individuals.  Little is understood about how latent Toxoplasma manipulates host cells during latent infection. We have shown that latent Toxoplasma imparts a unique transcriptional signature on infected host cells as compared to acute stage tachyzoites. By generating parasites that cannot export proteins into the host cell we show that many of these transcriptional changes rely on effectors to suppress type I interferon (IFN) and IFNγ signalling. Loss of the protein export abrogates transcriptional remodelling and prevents suppression of IFN signalling. Among the exported proteins, the inhibitor of STAT1 transcription (IST) plays a key role in limiting IFNγ signalling in bradyzoites. Furthermore, bradyzoite protein export protects host cells from IFNγ-mediated programmed cell death, even when export is restricted to latent stages. These findings highlight the functional importance of host manipulation in Toxoplasma's bradyzoite stages.