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Gene found in mice may play role in determining susceptibility to tuberculosis in humans

Boston, MA - Researchers from the Harvard School of Public Health studying tuberculosis resistance and susceptibility in animals have identified a gene in mice which plays a significant role in limiting the multiplication of intracellular pathogens Mycobacterium tuberculosis and Listeria monocytogenes inside host cells. The gene, Intracellular pathogen resistance 1 (Ipr1), found in the chromosome location known as sst1 (super susceptibility to tuberculosis 1), turns on a regulated cell death pathway of the bacteria-infected cells causing apoptosis and prevents catastrophic cell death, or necrosis. The findings appear in a paper in the April 7, 2005 issue of the journal Nature.

It is estimated that 8 million people are infected with tuberculosis annually with approximately 2 million of those dying from the lung disease per year. Yet only about 10 percent of people infected actually develop tuberculosis. Stress, malnutrition and other environmental factors significantly influence an individuals' susceptibility to developing the disease. In addition, genetic factors have been known to play an important role in determining outcomes of tuberculosis infection in human and other mammalian hosts. However, individual host resistance genes such as Ipr1, involved in innate immunity for tuberculosis, have been difficult to pinpoint, because of a highly complex multigenic control of host immunity.

The researchers studied which genes might influence an individuals' susceptibility to developing tuberculosis and found that an important genetic determinant of host resistance to tuberculosis is encoded within the region on mouse chromosome 1, which they named sst1. By identifying the Ipr1 gene within the sst1 region they believe they have uncovered a new mechanism that helps in limiting the possibility of developing M. tuberculosis, especially in the lungs.

Of interest, the Ipr1 gene also controls innate immunity to another intracellular pathogen Lister
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Contact: Kevin C. Myron
kmyron@hsph.harvard.edu
617-432-3952
Harvard School of Public Health
6-Apr-2005


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