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(Excerpted from The New York Times, Tuesday, June 20, 2006)

A common parasite's strongest asset: its stealth

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, including an estimated 50 million Americans. 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.

Strategies like this one have made Toxoplasma incredibly widespread and incredibly obscure. Mention the parasite to most people and chances are you will draw a blank. Pathogens that infect far fewer people, like the Ebola and West Nile viruses, are far more famous.

Toxoplasma's obscurity is in fact a great tribute to its powers. ''To the parasite's credit, it's incredibly successful,'' said Dr. Lloyd Kasper of Dartmouth University. ''It's adapted itself to be a benign infection.''

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. Kasper said.

Toxoplasma can, however, cause serious brain damage in those with weak immune systems, like fetuses and adults with AIDS.

Cats play a major role in the parasite's success. They can carry it in their intestines, where they can produce egglike cysts called oocysts. A single infected cat can shed 100 million oocysts in its droppings. The oocysts can survive in the soil for over a year and can contaminate drinking water.

Oocysts can infect humans, as well as 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 most pathogens by a tight barrier.

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 Dr. Barragan, an associate professor. But the scientists observed many of the parasites inside immune cells known as dendritic cells.

Dr. 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?'' Dr. Barragan said. He and his colleagues put dendritic cells in a dish and injected them with Toxoplasma. They noticed that the parasites triggered a peculiar change: the dendritic cells became hyperactive, crawling for an entire day.

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, Dr. Barragan and his colleagues could track the parasites as they spread.

Injecting dendritic cells carrying Toxoplasma spread the parasites to the brain and other organs far faster than injecting Toxoplasma alone. The researchers concluded that Toxoplasma was taking charge of the dendritic cells and riding along with them. Their results are published online in the journal Cellular Microbiology.

As Toxoplasma spreads through the body, it invades cells. Unlike other pathogens, Toxoplasma can enter almost every type of cell in the bodies of thousands 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.

David Sibley, an associate professor of molecular microbiology at Washington University in St. Louis, said, ''It just sits there, and the host doesn't recognize it as a foreign body it should destroy.''




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•   A common parasite's strongest asset: its stealth

The New York Times, Tuesday, June 20, 2006
Byline: Carl Zimmer

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