Discovering How Toxoplasma Hijacks Host Cells to Ride to the Brain

microscopic images of Toxoplasma
Dendritic cells have “podosomes” or feet that help them stay put (bright green blobs, arrowed). When infected with Toxoplasma (lower left), these go away, allowing the parasite to hijack the cells to migrate around the body. Removing TgWIP gene from the parasite restores the dendritic cells’ feet and stops the hijacking of the cell by the parasite. (Jeroen Saeij, UC Davis)

From the UC Davis Egghead Blog

For a tiny single-celled organism, Toxoplasma gondii (T. gondii) can wreak a lot of havoc. While this common parasite can infect all warm-blooded animals, often without obvious symptoms, it can cause serious complications and even death for infants born to mothers infected during pregnancy and for people with weakened immune systems.

In a paper out today in Cell Host & Microbe, a collaborative team led by UC Davis School of Veterinary Medicine researcher Jeroen Saeij identified one of the T. gondii genes responsible for how well the parasite survives in a host.

During the acute stage of infection, the Toxoplasma parasite hijacks immune cells to spread from the site of infection to distant organs and eventually the brain where it takes up long-term residence.

Using the gene-editing tool CRISPR, the researchers screened for candidate genes that may impact Toxoplasma migration. It was previously shown that Toxoplasma can enhance the motility of dendritic cells. These cells are part of the immune system, whose normal job is to go from the site of infection to the spleen and elsewhere throughout the body.

Saeij and his team focused on one mutant gene in T. gondiiknown as TgWIP, whose deletion affects the ability of the parasite to disseminate to distant organs.

“This TgWIP protein makes immune cells like a Trojan horse and allows T. gondii to move about,” Saeij said.

With the help of colleagues in Sweden, the UC Davis team created a knockout mutant T. gondii where TgWIP was removed. They infected mice with the mutant to study the parasite’s dissemination.

Researchers found zero brain cysts in the infected mice, showing that the deletion of TgWIP had a huge effect on the parasite’s ability to reach the brain.

“This looks like it could be the master regulator of Toxoplasma’s ability to hijack immune cells for its own benefit,” Saeij said. “We’re really excited about this. This gene is clearly important for the lifecycle of Toxoplasma and this discovery could be the building block for other researchers to develop novel treatments against Toxoplasma infection.”

Other authors on the paper are: at UC Davis, Patricia Pesavento, Lamba Omar Sangaré and Yifan Wang; Einar Ólafsson and Antonio Barragan, Stockholm University, Sweden; Ninghan Yang, Lindsay Julien, Ana Camejo and Sebastian Lourido, MIT; and Saima Sidik, Whitehead Institute for Biomedical Research. 

More information

In Vivo CRISPR Screen Identifies TgWIP as a Toxoplasma Modulator of Dendritic Cell Migration (Cell Host & Microbe)

 

 

 

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