WEHI researchers have found out how dormant Toxoplasma Parasites in the brain manipulate their host cells to ensure their own survival.
The researchers showed that the parasites are able to go dormant and undetected in neurons (brain cells) and muscle cells by releasing proteins that turn off the cells’ ability to alert the immune system. With know-how and technologies from the Advanced Genomics Facility and the Center for Dynamic Imaging from WEHI, they were able to visualize the parasites in real time.
The discovery provides a better understanding of how Toxoplasma Parasites can hide in the brain, causing them to reactivate and cause disease. It could pave the way for new drug targets to treat patients suffering from chronic toxoplasmosis infections.
The research conducted by Dr. Simona Seizova, PhD student Ushma Ruparel, Associate Professor Chris Tonkin and colleagues from WEHI was published in the journal Cell host & microbe.
At a glance
- Researchers have figured out how dormant Toxoplasma gondii Parasites manipulate host cells in the brain to promote their own survival.
- They showed that dormant parasites (called bradyzoites) exported proteins to suppress immune signals in infected host cells and hide undetected.
- The discovery could pave the way for new treatments for chronic toxoplasmosis infections.
A “molecular battle” for survival
Toxoplasmosis is a parasitic infection that affects humans and other mammals. It is caused by eating undercooked or contaminated meat and coming into contact with infected cat feces.
Around one in five Australians is infected with Toxoplasma gondii, the parasite that causes toxoplasmosis. Toxoplasma Infection can cause congenital birth defects, blindness, and neurological dysfunction in unborn children. It can lead to blindness and even death in immunocompromised adults.
PhD student Ushma Ruparel said Toxoplasma Parasites often rest in the host animal’s brain, where they can reactivate and cause serious illness.
“We know that Toxoplasma Parasites produce their own molecules and proteins that they export to the host cell to protect themselves from detection by the immune system. While this is well understood in the acute initial stages of infection, how? Toxoplasma kidnapped its host cells in its dormant form was unknown, ”said Ms. Ruparel.
“With our colleagues, who have expertise in genomics and advanced imaging, we have shown that the parasite exports proteins called inhibitors of STAT1 transcription (IST) into the host cell in order to suppress immune signals.”
Associate Professor Tonkin said that IST has played a key role in limiting interferon signaling in bradyzoites to protect host cells from the immune-mediated cell death that is essential to the body’s fight against Toxoplasma.
“Interferon is the beacon molecule of the immune system. It gives off a blinking sign to let the immune system know that the body has been infected with a number of diseases, including Toxoplasma,” he said.
“Interferon is crucial in the fight against disease. However, the ripped parasite tries to turn off this signal during the latency period as this is the only way it can survive. While the immune system is determined to rid the body of the infection, the parasite only has survival in its head. So it’s essentially a tug-of-war, a molecular battle. “
Link to neurological diseases
While the exact mechanism of why and how the pathogen is reactivated to cause disease is poorly understood, there appears to be a link between people with immunodeficiency and brain lesions.
The association of Toxoplasma Having neuropsychiatric illnesses for the past decade is another curious element of that illness, said Associate Professor Tonkin.
“Although there is a connection between Toxoplasma Infections and schizophrenia, bipolar disorder and other neurodegenerative diseases like Alzheimer’s are still not a cause because we don’t know the cause and effect, ”said Associate Professor Tonkin.
“The way this parasite resides in our brains during chronic infection and how it turns off our innate immune systems to survive is quite unique. Although this work has all been done in the laboratory, it will lay the foundation for bringing us closer to these age-old questions of how these pathogens affect our nerve tracts and what their exact role is.
“Our next step is to find out what chronic infections are all about that makes these changes truly unique to chronic infections. We found a particular parasite protein that seems to play a role, but it doesn’t seem to explain all of the changes, and we want to see if there are others. “
Addressing an Important Health Stress
The results have begun to unravel the molecular actors that help pathogens create latency, which could pave the way for a better understanding of the effects of parasites on the brain.
Associate Professor Tonkin said latent infections are one of the biggest global health burdens.
“Diseases like HIV, hepatitis, malaria, and tuberculosis are examples of chronic or latent infections that have significant disease, disability, and economic impact. If we can understand what reactivates these latent infections and how they control our cells and brains, we will be on the way to discover new treatments that will reduce this burden on some of the most deprived people around the world. “
This research was supported by the Australian National Health and Medical Research Council, the David Winston Turner Endowment Fund, and the Victorian Government.