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Leishmania mutant provides insight into disease and may lead to a vaccine

ed this problem by developing a mutated parasite incapable of causing disease. This enabled the team to begin studying the animals about one week after infection.

They tested the engineered parasites in sand flies, which are responsible for transmitting the parasite to humans. The team also examined the parasites in immune cells called macrophages, which normally protect the body but are the cells that house the Leishmania parasites responsible for causing disease in mammals.

Compared to normal parasites, the mutants showed a 10-fold lower survival in the sand flies after three days, after which point they were completely eliminated. They also were unable to survive in macrophages.

Next, the investigators injected the parasites into mice that were genetically susceptible to leishmaniasis. As expected, the animals did not become sick, suggesting that the parasites had not survived. Surprisingly, though, parasites were in fact found in tissue samples from these mice.

"This was so unexpected that at first we didn't believe it," Beverley says. "But we and others have confirmed it."

Since the mutated parasites did not survive in macrophages, the investigators have no idea what type of cell did allow them to survive, and they are working to answer that question. They then will look for parasites in the same kinds of cells during normal infection.

"This will tell us if our mutant is a good model for studying normal persistent infections," Beverley says.

The researchers also are investigating whether the mutant parasite might help develop a vaccine against leishmaniasis, as many studies suggest that the key to parasite vaccination may lie in understanding how persistent parasites interact with the immune system.

"Those studies are early," Beverley says, "but they look promising."


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Contact: Gila Z. Reckess
reckessg@msnotes.wustl.edu
314-286-0109
Washington University School of Medicine
28-Aug-2003


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