UA researchers hope to cure diseases with a common brain parasite

A mouse brain genetically engineered to show green where Toxoplasma Gondii has infected the brain.

There might be a parasite in your brain.

It’s estimated that up to one-third of the world’s population is infected with the brain parasite Toxoplasma gondii.

The U.S. has a relatively low rate of infected people, estimated to be between 10 and 25 percent. Countries such as France have an infection rate of 60 to 80 percent.

As far as parasites go, Toxoplasma gondii isn’t’ that bad, unless you’ve had a transplant and are left immunocompromised. Folks who have a weakened immune response can suffer brain damage and even death if infected with toxoplasmosis.

University of Arizona researchers are studying whether the unique relationship between the parasite and the brain could lead to breakthroughs in understanding Alzheimer’s and other brain-related illnesses..

“There are very few microbes that can persist in the brain without causing symptoms,” said Dr. Anita Koshy, a research physician at the University of Arizona who studies Toxoplasma gondii..

How it responds in the body Toxoplasma gondii can exist within the brain for the lifespan of its host because of how it interacts with the body’s immune response. Healthy adults will show no symptoms because their immune systems keep the parasite from damaging the brain..

Infected neurons glow green, and the parasite living in the cell glows red.

“Toxo knows how to change the brain in a positive way that allows the parasite to persist, which we presume means it tunes down the immune response to toxo in the brain,” said Koshy.

“There is a lot of literature that suggest the immune response, in things from stroke to Alzheimer’s to MS to Parkinson’s disease is actually what causes the problems in those diseases and disorders," she added. "If we can learn how the parasite manipulates the brain immune response, maybe we can do it for the same reason.”

Koshy wants to understand how Toxoplasma gondii avoids being attacked by the body’s immune response. Infected brain cells are changed by the parasite so that it can survive.

They think toxo might completely block out the immune response. Another theory is that the parasite silences the cell it’s infecting, not allowing it to call out for help to nearby cells.

What’s certain is that toxo keeps itself alive by keeping the immune response in check and vice-versa. This is how it’s able to persist throughout the lifespan of its human hosts. When a person’s immune system is no longer able to keep a front with toxo, the host becomes ill and can die.

“A lot of people are infected with toxo. We think it doesn’t have any problems except in those who end up being immunocompromised,” said Koshy.

“So, if they end up getting AIDS, or get a bone marrow transplant, or if they’re infected when they’re a fetus," she continued, "then it can have huge problems in the brain. There’s no known way to cure toxo.”

Genetically engineered mice and parasite allow Koshy’s research lab to see how the parasite effects the brain.

What the studies show
Koshy and her lab use mice to study how Toxoplasma gondii interacts with the brain’s immune response. The infected mice are engineered to express a green-colored protein within their brain cells when infected with parasite proteins.

“Using mice allows us to track the cells and figure out which cells interact with the parasite. We can pull those green cells out and molecularly dissect how the parasite has modified that specific cell, compared to the cell that’s next to it,” Koshy said.

There are three studies on mice that showed being chronically infected with Toxoplasma gondii made the mice more resistant to central nervous system inflammation, the same type of inflammation that occurs in stroke and Alzheimer’s patients.

“Toxo is one of those parasites that can infect the brain and effectively hide from the immune response,” said Oscar Mendez, a graduate student in Koshy’s lab.

Toxoplasma gondii’s primary hosts are cats — the only known mammals that allow the parasite to reproduce. The parasite offspring are found with cat feces. After a gestation period, they release a spore that will infect a new host.

Mendez studies the behaviors of mice infected with toxo. His theory: The parasite might change the brain chemistry in mice, luring them to cat urine. This would make them an easier target for cats. He believes the parasite does this to infect its primary host.