A parasite that might already be residing in your brain seems capable of infecting the very immune cells meant to fight it off. New research from UVA Health sheds light on how the body manages to keep this infection in check.
Toxoplasma gondii is a potentially harmful parasite that affects warm-blooded animals. Humans typically come into contact with it through interaction with cats, consuming contaminated fruits or vegetables, or eating undercooked meat. Once inside the body, the parasite can spread to various organs and ultimately take up residence in the brain, where it may linger for a lifetime. It’s estimated that about a third of people worldwide carry Toxoplasma, but most never experience any symptoms. When symptoms do arise, known as toxoplasmosis, it’s particularly severe for individuals with weakened immune systems.
Researchers, led by Tajie Harris, PhD, sought to uncover how the immune system reacts when Toxoplasma invades CD8+ T cells—specialized immune cells that are designed to eliminate infected cells.
“We understand that T cells are crucial for fighting off Toxoplasma gondii, and we thought we had a good grasp of the reasons behind it. T cells can destroy infected cells or signal other cells to target the parasite. However, we discovered that these same T cells can become infected, and if that happens, they may choose to self-destruct. Since Toxoplasma needs to live within cells, the death of the host cell is essentially the end for the parasite,” explained Harris, who is the director of the Center for Brain Immunology and Glia at UVA School of Medicine. “Understanding the immune response to Toxoplasma is critical for various reasons, especially since immunocompromised individuals are at higher risk for this infection. Now we have deeper insights into how we can support these patients in their fight.”
Caspase-8 and the Self-Destruct Defense
Harris and her team found that CD8+ T cells depend on a key enzyme, caspase-8, to control T. gondii. This enzyme is vital in regulating immune responses and can activate a mechanism that leads to cellular self-destruction.
In laboratory tests, mice lacking caspase-8 in their T cells showed significantly higher levels of T. gondii in their brains compared to those whose T cells produced the enzyme, despite both groups having robust immune responses against the infection.
The contrasting outcomes were notable. Mice with caspase-8 remained healthy, while those without it suffered severe sickness and even death. Analysis of their brain tissue indicated that their CD8+ T cells were much more susceptible to the parasite.
These results highlight the crucial function that caspase-8 serves in limiting T. gondii within T cells. Moreover, they contribute to the growing body of evidence that this enzyme is broadly essential for managing infectious challenges.
“We reviewed existing scientific literature for cases of pathogens infecting T cells. There were surprisingly few,” remarked Harris, who is part of UVA’s Department of Neuroscience. “We believe we now understand why. Caspase-8 leads to T cell death, meaning only the pathogens that have adapted to interfere with caspase-8 can survive in CD8+ T cells. Before our research, we had no clue just how important caspase-8 was for safeguarding the brain from Toxoplasma.”
Study Details and Funding
The findings appeared in the journal Science Advances. The research team included Lydia A. Sibley, Maureen N. Cowan, Abigail G. Kelly, NaaDedee A. Amadi, Isaac W. Babcock, Sydney A. Labuzan, Michael A. Kovacs, Samantha J. Batista, John R. Lukens, and Harris. The scientists reported no financial conflicts of interest.
Funding for the study was provided by the National Institutes of Health, through various grants, along with support from a University of Virginia Pinn Scholars Award, a UVA Shannon Fellowship, and UVA’s Strategic Investment Fund.
