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Newly identified mechanism helps explain why people of African descent are more vulnerable to TB

Boston, MA -- A team of scientists has identified a cellular mechanism that may help explain the puzzle of why people of African descent are more susceptible to tuberculosis infection and why, once infected, they develop more severe states of the disease than whites. The team includes researchers from University of California, Los Angeles (UCLA), and Harvard School of Public Health (HSPH). The paper will appear online in the February 23 issue of Science Express.

Approximately eight million people worldwide are infected with TB annually, with an estimated two million people dying from the lung disease each year. TB is caused by the pathogen Mycobacterium tuberculosis, but infection does not automatically result in full-blown disease. In the U.S., minority and foreign-born populations have significantly higher rates of TB than the overall U.S. average, according to the Centers for Disease Control and Prevention. In 2004, African Americans had TB case rates that were eight times higher than whites.

Scientists have understood that mice -- a frequently used animal model in experiments -- combat microbes such as TB by producing nitric oxide in scavenger cells of the immune system known as macrophages. However, this mechanism is not prominent in humans, and the mechanism by which human macrophages kill the tubercle bacillus has remained an additional puzzle. Innate immunity is the rapid immune response of host scavenger cells to recognition of certain patterns of molecules found on pathogens, which has been retained in evolution from fruit flies to humans. A set of receptors on macrophages in humans called Toll-like receptors contribute to innate immune responses. The researchers describe a novel pathway used by human macrophages that may be critical to resisting infection with certain pathogens and that turns out to be critically dependent on vitamin D. This description provides a different way to think about how human immune systems battle pathogens in
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Contact: Robin Herman
rherman@hsph.harvard.edu
617-432-4752
Harvard School of Public Health
24-Feb-2006


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