Toxoplasma parasite hijacks immune cells but body has kill switch

A parasite can hijack the very cells sent to kill it

The Toxoplasma gondii parasite can infect the specialized immune cells tasked with destroying it. New research from UVA Health reveals how the body's defenses still manage to keep this common brain infection in check.

Roughly one third of the global population is believed to carry the parasite. People are typically exposed through contact with cats, contaminated produce, or undercooked meat.

After infection, the parasite can spread to multiple organs and settle in the brain for life. Most carriers never develop symptoms, but the resulting illness, toxoplasmosis, is dangerous for people with weakened immune systems.

Immune cells have a self-destruct button

Researchers led by Dr. Tajie Harris investigated how the immune system responds when T. gondii invades CD8+ T cells. These are the immune cells responsible for killing infected cells.

"We found that these very T cells can get infected, and, if they do, they can opt to die," said Harris, director of UVA's Center for Brain Immunology and Glia. "Toxoplasma parasites need to live inside cells, so the host cell dying is game over for the parasite."

The team discovered these T cells rely on a powerful enzyme called caspase-8 to control the parasite. This enzyme can trigger a process that causes an infected cell to self-destruct.

Mice without the enzyme died quickly

In lab experiments, mice whose T cells lacked caspase-8 developed far higher levels of T. gondii in their brains compared to normal mice. This occurred despite both groups mounting strong immune responses.

The outcome was severe. Mice with the enzyme remained healthy. Mice without it became severely ill and died.

Examination of brain tissue showed that CD8+ T cells in the enzyme-deficient mice were much more likely to be infected. This indicates caspase-8 is crucial for limiting the parasite inside T cells.

The finding explains a rare phenomenon

The research, published in Science Advances, adds to evidence that caspase-8 is broadly important for controlling infectious threats. It also solves a mystery.

"We scoured the scientific literature to find examples of pathogens infecting T cells. We found very few examples," Harris said. "Now, we think we know why. Caspase-8 leads to T cell death."

The implication is that only pathogens which have evolved ways to interfere with caspase-8 can survive inside these immune sentinels. Before this study, scientists did not know this enzyme was so critical for protecting the brain from Toxoplasma.

Key facts about Toxoplasma gondii

• It is a parasite that infects warm-blooded animals.
• An estimated one third of people worldwide carry it.
• Common exposure routes include:
  • Contact with cat feces
  • Eating contaminated fruits or vegetables
  • Eating undercooked meat
• It forms lifelong cysts in the brain.
• Serious illness (toxoplasmosis) primarily threatens immunocompromised individuals.

Understanding this immune mechanism is vital for helping vulnerable patients fight the infection. The research team reported no financial conflicts of interest.

Funding was provided by multiple National Institutes of Health grants and awards from the University of Virginia.