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Improving the body's 'homeland security' against TB

The microbe that causes tuberculosis operates the way a human terrorist would. With minimal resources, the TB bacterium skillfully blends in and gains strength before lashing out unexpectedly. This microbe, which claims more human lives each year than any other bacterial pathogen, even uses its host's defenses, hiding out in an immune cell called a macrophage.

Now, Rockefeller scientist John MacMicking, Ph.D., has discovered a unique way the immune system can disarm the bacterial offender. If this defense could be strengthened, TB could be brought to biological justice.

Reporting in the October 24 issue of the journal Science, Rockefeller researchers MacMicking and John McKinney, Ph.D., with their colleague from Duke University, Greg Taylor, Ph.D., have identified a new pathway stimulated by the soluble host protein called interferon-gamma that impairs TB's ability to reproduce itself in mice. Interferon-gamma primarily instructs immune cells to perform different tasks by helping turn on or off certain genes. In the case of interferon-gamma, literally hundreds of genes are induced once its signal is transmitted to the nucleus of the activated cell. Of these, only a few will be responsible for controlling the replication of the TB bacterium. Finding those genes involved in antimicrobial activity against TB is the key.

"We're looking for immune pathways which could render the TB bacillus vulnerable," says MacMicking, a research associate in the Laboratory of Infection Biology and lead author of the Science paper. "By learning more about how the immune system successfully operates during infection, we may soon be able to manipulate the host-pathogen relationship in a way which favors us, a somewhat reluctant host."

MacMicking and colleagues discovered the pathway, called LRG-47, based on clues from another TB-inhibiting pathway called NOS2 and analysis of mouse genes turned on during TB infection. MacMicking is already homing in on t
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Contact: Lynn Love
lovel@rockefeller.edu
212-327-8977
Rockefeller University
23-Oct-2003


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