A staggering 30-50% of the world’s population is estimated to be infected with the parasite Toxoplasma gondii
. This parasite is known to invade the brain and affect behaviors, but until recently, researchers had no idea how the organism crossed the blood-brain barrier. Using a powerful multi-photon imaging technique, researchers record for the first time how “Toxo” hijacks into the brain by way of endothelial cells.
, also known colloquially as “Toxo,” can infect virtually any warm-blooded animal. However, the parasite can only undergo sexual reproduction in domesticated cats, and so most people know Toxo as the disease that humans can get from changing and accidentally ingesting contaminated cat litter.
Toxoplasmosis, the disease caused by Toxo, can be life threatening for people with compromised immune systems, such as infants, cancer patients, or HIV/AIDS patients. In addition, pregnant women can transmit the parasite to their unborn baby. Toxo invasion of the brain has been linked to adverse behavioral changes, though no one really knew how the parasite sneaked across the protective barrier in the brain.
"Crossing the blood-brain barrier is a rare event in part because this structure is designed to protect the brain from pathogens," said Christopher Hunter, senior study author and the Mindy Halikman Heyer President's Distinguished Professor at Penn Vet. "And yet it happens and we have now been able to visualize these events. It's something that no one had seen before."
Using innovative imaging techniques with the multi-photo microscope, the team at Penn filmed exactly how Toxo invades the brain. The team used mice engineered to have green fluorescent endothelial cells, which make up the lining of blood vessels. They then infected these mice with a modified form of Toxo that glows red.
The video shows how Toxo squeezes its way in through the endothelial cells. And after two weeks, the researchers saw Toxo bursting out of infected endothelial cells and invade into the brain tissues next to the green cells.
The team also performed subsequent experiments, which showed that Toxo invasion of the blood-brain barrier happens independent of other carrier cells, dispelling the so-called Trojan horse hypothesis.
Another interesting finding was the surprising number of Toxo parasites that existed as free floaters in the blood. They found that free parasites in the mouse blood made up about a third of the total parasite load. But the good news is that this parasite load in the blood was gone in about 10 days time, suggesting a transient nature.
"From a treatment perspective," Hunter said, "that means if a pregnant woman gets infected for the first time, there is a fairly short period of time when the parasite can cross the placenta and affect the fetus. That tells us that targeting these stages in the blood during this narrow window could be effective at preventing congenital transmission."
Now that scientists know how Toxo invades the brain, they have better targets for treating and preventing the parasite infection. This mode of action could also give scientists fresh insight as to how Toxo influences human behaviors, and even cause psychiatric diseases like schizophrenia as some research have suggested. The mechanisms behind Toxo’s invasion may also illuminate how other pathogens breach our defense to the brain.
Additional sources: Nature Microbiology