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Trudeau Institute announces discovery on tuberculosis

October 18, 2011
By PETER CROWLEY - Managing Editor ( , Adirondack Daily Enterprise

SARANAC LAKE - Research from Trudeau Institute opens a new door for those who make vaccinations against tuberculosis.

Saranac Lake scientist Andrea Cooper's lab has discovered how lymphoid tissue that forms in the lungs during chronic inflammation is connected to the way the body fights TB. The new data will be published in the Nov. 1 issue of The Journal of Immunology (Vol. 187, No. 10) and is available now online. Shortly after Trudeau Institute announced the news Tuesday, Cooper spoke to the Enterprise to explain a research project she's been working on since 2006.

"It gives us a new target activity for vaccination that may improve protection," Cooper said.

Article Photos

New lymphoid tissue in the lung is shown in green, and the red indicates Cxcl13 that Trudeau Institute scientist Andrea Cooper thinks brings protective cells to the infected part of the lung. In the normal response, there are large areas of lymphoid tissue generating lots of Cxcl13, but not in the defective response when scientists did not have a molecule Interleukin 23 is absent.
(By Mike Tighe, manager, Imaging Core Facility, Trudeau Institute)

TB, a deadly disease worldwide, is caused by infection with Mycobacterium tuberculosis. It normally attacks the lungs but can also affect other parts of the body. It is spread through the air when people with active TB infection cough, sneeze or otherwise transmit their saliva through the air. Left untreated, TB can kill more than 50 percent of its victims.

The village of Saranac Lake was established in the late 1800s as a TB cure center, the first in North America, but its leading industry faded when drugs began curing TB in the 1940s. In the early 1960s, Trudeau Institute emerged from the ashes of the shuttered Trudeau Sanitarium, the village's leading institution which had been established by pioneering physician and scientist Dr. Edward Livingston Trudeau.

When a lung is inflamed for a long period of time, as with TB, new lymphoid tissue develops, but scientists didn't know much about it, Cooper said.

"We just didn't know what it was for, what this lymphoid tissue is doing, whether it was good or bad," she said.

"So, there's blood vessels that go through your lung, and that's where the cells that are coming into your lung to control the infection are," she continued. "As they go through the blood vessels, the infectious tissue in the lung sends a signal to the blood vessels ... and gets the cells to come out of the blood and into the tissue.

"We found that when we didn't have the lymphoid tissue, the cells ... get stuck around the blood vessel. ... They don't get to the infected site. They lose their sense of direction."

Why was that? Her lab discovered a link with a specific kind of cytokine (aka interleukin) called Interleukin 23 in the lymphoid tissue.

"Cytokine is a chemical that acts between cells," Cooper said. "One cell will produce it, and another cell recognizes that it's there, and it's an information carrier."

When Interleukin 23 isn't there, her lab determined, neither is Cxcl13, "and that's the molecule that we think brings the cells out of the blood to the site of the infection," she said.

How vaccine makers will use this discovery is complicated by the way TB works. Rather than blocking the body's immune system, the disease encourages it so the protective blood cells can break apart the lung tissue, giving the bacteria room to spread around.

"It wants damage to occur," Cooper said.

Still, according to Trudeau's press release, "By understanding how different components of the immune response control the bacteria that cause tuberculosis, doctors and public health officials will be better positioned to protect against the disease with a combination of vaccination, immunotherapeutics and drugs."

Others who contributed to the project included scientists now with the University of Pittsburgh and the University of Rochester, as well as Shabaana Khader, Javier Rangel-Moreno and Troy Randall. Cooper's studies are funded by Trudeau Institute and grants from the National Institutes of Health.



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