WEHI researchers have discovered how brain-based Toxoplasma parasites survive by manipulating cells in their host’s brain.

Around one in five Australians are infected with Toxoplasma gondii, the parasite that causes toxoplasmosis. If first infected when pregnant, Toxoplasma infections can lead to birth defects, blindness and neurological dysfunction in unborn children. In adults who are immunocompromised, reactivation of a dormant infection can cause blindness and even death.

Undetected and in control

WEHI researchers have explained how dormant Toxoplasma parasites can hide undetected in the brain and manipulate cells to foster their own survival. The discovery paves the way for finding new drug targets in order to treat patients suffering from chronic toxoplasmosis infections.

Dr Simona Seizova, who undertook the research as her PhD project at WEHI, said the team showed that bradyzoites – dormant parasites – deployed proteins called Inhibitor of STAT1 transcription (IST) to silence the immune system.

“We revealed that bradyzoites continue to hijack their host and protect themselves from immune attack long past the initial stages of infection. By deploying their IST molecule, bradyzoites suppress immune signals and hide undetected,” she said.

Neurological triggers

The association of Toxoplasma with neuropsychiatric conditions over the past decade is fascinating yet mysterious, said Associate Professor Chris Tonkin.

“While we know there is a correlation between Toxoplasma infection and schizophrenia, bipolar disorder and other neurodegenerative conditions such as Alzheimer’s disease, we don’t know the cause and effect.

“The way this parasite resides in our brains during dormant infection and the way that it shuts down our immune system to survive is quite unique.

“It’s exciting because the foundational work we’ve conducted in the laboratory is bringing us closer to understanding age-old questions about how these pathogens interfere in our neural pathways, and what their exact role is.”

Broader burden of disease

The team’s findings have started to reveal the key molecular players that help pathogens generate a latent infection. Associate Professor Tonkin said latent infections were one of the biggest health burdens in the world.

“Diseases such as HIV, hepatitis, malaria and tuberculosis are all examples of chronic or latent infections that cause significant disease, disability and economic impact,” he said.

“Understanding what triggers latent infections to reactivate their control over our cells will steer us towards finding new treatments for diseases impacting some of the most underprivileged communities in the world.