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This is an archive article published on June 24, 2006

Clever hazard

A common parasite reveals its strongest asset—stealth

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On paper, Toxoplasma gondii looks as if it ought to be the most famous parasite on earth. This single-celled pathogen infects over half the world’s population. Each of Toxoplasma’s victims carries thousands of the parasites, many residing in the brain. As if that were not enough of an accomplishment, Toxoplasma is equally adept at infecting all other warm-blooded animals, as disparate as chickens and kangaroos.

Scientists are now discovering some of the secrets of Toxoplasma’s success. Researchers in Sweden report that the parasite fans out through the body by manipulating mobile cells that are part of the immune system. Toxoplasma hijacks these so-called dendritic cells and makes them race around the body and ignore commands from other immune cells to commit suicide. The dendritic cells sneak the parasites into the brain and other organs, acting much like a Trojan horse.

For the vast majority of people, Toxoplasma causes no serious effects. It manages this feat by hijacking our cells and immune system, and establishing a careful harmony between parasite and host. “Once you get infected with Toxoplasma, you’re infected for life,” Dr Lloyd Kasper of Dartmouth University said. Toxoplasma can, however, cause serious brain damage in those with weak immune systems, like fetuses and adults with AIDS.

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Cats play a major role in the parasite’s success. They carry it in the intestines, where they produce egglike cysts called oocysts. A single infected cat can shed 100 million oocysts in its droppings. Oocysts can infect humans, other mammals and birds. Undercooked pork, chicken and other meat is another route Toxoplasma can take into our bodies.

Once Toxoplasma enters a host, it spreads quickly. Within hours it can be detected in the heart and other organs. It is even able to infect the brain, which is protected from pathogens by a tight barrier.

Dr Antonio Barragan and his colleagues at the Karolinska Institute in Stockholm were puzzled at first about how Toxoplasma managed this swift journey. “When we looked for parasites in the blood, we found very few that were just swimming around,” said Barragan. But the scientists observed many of the parasites inside immune cells known as dendritic cells. Barragan was intrigued.

Dendritic cells, common in the gut, often come into contact with pathogens. They respond by crawling to the lymph nodes or the spleen, where they communicate with other immune cells. “That led us to think, what if this parasite is directing these cells to move and to disseminate through the body?” Barragan said. His team put dendritic cells in a dish and injected them with Toxoplasma. They noticed the parasites triggered a peculiar change: the dendritic cells began crawling for an entire day.

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Next, the scientists observed how Toxoplasma spread through a living animal. They added a firefly gene to the parasites so that they produced a glow. When they injected the parasites into mice, a little of the light escaped from the animals. By putting the mice in a darkened box, Barragan and his colleagues could track the parasites as they spread. The results were published online in Cellular Microbiology.

As Toxoplasma spreads through the body, it invades cells. Unlike other pathogens, it can enter almost every type of cell in the bodies of host species. The parasite slips into a cell by latching onto its surface and pulling the membrane over itself. “You can think of it like sticking your finger into a balloon,” said Vernon B. Carruthers of the University of Michigan.

“This is an organism that has very cleverly worked out a way to go from one host to another,” said Alan Sher, chief of the Laboratory of Parasitic Diseases at the National Institutes of Health. In the early stages of infection, the parasite sets off the production of signalling molecules called cytokines. They cause the immune system to attack Toxoplasma, killing off free-floating parasites. The parasites that happen to be inside cells during the attack somehow recognise what is happening and enter a kind of hibernation. Their host cell turns into a cyst in which they hide from the immune system. —

CARL ZIMMER

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