The parasite that may already live in your brain can infect the very immune cells trying to destroy it, but new UVA Health research reveals how our bodies keep it under control.
The parasite, Toxoplasma gondii, is potentially deadly. It infects warm-blooded animals, but it's typically passed to people by cats or by consuming contaminated produce or undercooked meat. Once it's made its way inside you, the parasite spreads throughout your body and takes up permanent residence in your brain. It's estimated about a third of all people around the world have the parasite, yet, amazingly, few ever have symptoms. The disease it can cause, toxoplasmosis, is primarily a problem for people who are immunocompromised.
Researchers led by Tajie Harris, PhD, have determined how our immune systems fight back against the parasite when it makes it inside the CD8+ T cells meant to destroy it.
"We know that T cells are really important for combatting Toxoplasma gondii, and we thought we knew all the reasons why. T cells can destroy infected cells or cue other cells to destroy the parasite. We found that these very T cells can get infected, and, if they do, they can opt to die. Toxoplasma parasites need to live inside cells, so the host cell dying is game over for the parasite," said Harris, the director of the Center for Brain Immunology and Glia (BIG Center) at the University of Virginia School of Medicine. "Understanding how the immune system fights Toxoplasma is important for several reasons. People with compromised immune systems are vulnerable to this infection, and now we have a better understanding of why and how we can help patients fight this infection."
Battling the Brain Parasite
Harris and her collaborators discovered that our CD8+ T cells have a potent weapon against T. gondii: an enzyme called caspase-8. Caspase-8 is an important regulator of our immune systems, and one of its jobs is to cause cells to self-destruct.
The UVA researchers found that lab mice that lacked Caspase-8 in their T cells had far greater numbers of T. gondii parasites in their brain than did mice that had the enzyme. This was the case even though both sets of mice produced strong immune responses to deal with the infection.
While the mice with the enzyme continued living normally, the ones without grew sick and died. Examining their brains after their deaths revealed that their CD8+ T cells were much more likely to be infected with the parasites.
That suggests that Caspase-8 is a critical player in how our bodies control T. gondii within our T cells. And it also adds to a growing understanding of the importance of the enzyme in controlling pathogens in our bodies more generally, the researchers report in a new scientific paper.
"We scoured the scientific literature to find examples of pathogens infecting T cells. We found very few examples," said Harris, part of UVA's Department of Neuroscience. "Now, we think we know why. Caspase-8 leads to T cell death. The only pathogens that can live in CD8+ T cells have developed ways to mess with Caspase-8 function. Prior to our study, we had no idea that Caspase-8 was so important for protecting the brain from Toxoplasma."
Findings Published
Harris and her colleagues have published their findings in the scientific journal Science Advances. The research team consisted of 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 have no financial interest in the work.
The research was supported by the National Institutes of Health, grants R01NS112516, R01NS134747, R21NS12855, T32GM008715, T32AI007496, T32AI007046, T32NS115657, F30AI154740, T32AI007496 and T32GM007267; a University of Virginia Pinn Scholars Award; a UVA Shannon Fellowship; and UVA's Strategic Investment Fund.
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