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LIAI scientists identify immune system trigger for fighting Lyme disease

Research could lead to new vaccines against Lyme disease and other bacterial infections

Researchers at the La Jolla Institute for Allergy & Immunology (LIAI) today announced an important finding on Lyme disease that could eventually lead to the development of a new vaccine to prevent this tick-borne disorder. Lyme disease is transmitted to humans by the bite of infected ticks. Typical symptoms include fever, headache, fatigue, and sometimes skin rashes. If left untreated, it can spread to the joints, the heart and the nervous system and can lead to serious health problems.

LIAI scientist Mitchell Kronenberg, Ph.D., and an international team of scientists, have identified that Borrelia burgdorferi, the bacteria that causes Lyme disease, contains a glycolipid which triggers an immune response from the body's natural killer (NK) T cells, a type of white blood cell. The finding is particularly exciting because it is one of the few glycolipids found to naturally induce an immune response from the body's NK T cells, which are prized for their ability to initiate a fast and vigorous attack against infection. Scientists are hopeful that this glycolipid can be used to create a vaccine against Lyme disease.

The finding was published today in the online version of the scientific journal Nature Immunology in a paper entitled, "Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria."

This was the second major finding on NK T cells published in the last year by Kronenberg and his team. In a June 2005 scientific paper in Nature, Kronenberg and colleagues identified a bacteria, Sphingomonas, as containing a glycolipid which also triggers an NK T cell response. Now that a total of three substances have been found to naturally activate the NK T cells, "it opens up the idea that we should be looking at many different types of bacteria that may be able to activate these cells," Kronenberg said.

Most white blood cells respond to foreign proteins to protect the body, but NK T cells are unique in that they respond to glycolipids, which are natural biochemicals made of linked fat and sugar. Prior to Kronenberg's findings, only one compound, developed by the Kirin Pharmaceutical Research company in the1990s, was known to activate the NK T cells. In a surprising twist, that compound was initially discovered in marine sponges. The compound was found to have anti-tumor activity and is currently in clinical trials for several tumor types. Because the NK T cells are known to be responsible for the tumor fighting mechanism induced by the marine sponge compound, and because their mechanism of action has been so mysterious, the NK T cells have generated increased research interest over the last several years.

In particular, scientists wanted to know what substance would naturally activate the NK T cells. "Although the synthetic compound was useful for many studies, we wanted to know what substance would normally cause the NK T cells to produce an immune response, and it was not believable that marine sponges normally stimulate our immune system," said Kronenberg, who is also LIAI's President and Scientific Director.

After identifying the Sphingomonas bacteria last year as an NK T cell activator, Kronenberg strongly suspected that other bacteria might also activate these cells, which led to the discovery of the Borrelia burgdorferi antigen. He believes many other types of bacteria may also produce an immune response from NK T cells. "This is an exciting possibility that needs to be further explored as it could lead to the development of vaccines or treatments for many bacteria caused diseases," he said.

Scientists from the Scripps Research Institute, Rockefeller University, the National Institutes of Health, Albany Medical College, Harvard Medical School, and Industrial Research Ltd of New Zealand also participated in the study.

Bonnie Ward | EurekAlert!
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