Scientists ID Novel Pathway for T-Cell Activation in Leprosy

UCLA researchers and colleagues have pinpointed a new mechanism that potently activates T-cells, the group of white blood cells that plays a major role in fighting infections. In work published March 25, 2012 online in Nature Medicine, the team specifically studied how dendritic cells, immune cells located at the site of infection, become more specialized to fight the leprosy pathogen known as Mycobacterium leprae. Dendritic cells, like scouts in the field of a military operation, deliver key information about an invading pathogen that helps activate the T-cells in launching a more effective attack. It was previously known that dendritic cells were important for a strong immune response and the number of such cells at an infection site positively correlated with a robust reaction. However, until now it was poorly understood how dendritic cells become more specialized to address specific types of infections. The researchers found that a protein called NOD2 triggers a cell-signaling molecule called interleukin-32 that induces general immune cells called monocytes to become specialized information-carrying dendritic cells. "This is the first time that this potent infection-fighting pathway with dendritic cells has been identified, and demonstrated to be important in fighting human disease," said the study's first author Dr. Mirjam Schenk, postdoctoral scholar, division of dermatology, David Geffen School of Medicine at UCLA. In conducting the study, scientists used monocytes taken from the blood of healthy donors and leprosy patients and incubated the cells with the pathogen M. leprae or specific parts of the mycobacteria, known to trigger NOD2 and TLR2, both associated with immune system activation.
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