Pushpa Jayaraman, PhD

American Lung Association Scholar: Tuberculosis

Pushpa Jayaraman, PhD, is studying a novel mechanism to kill Mycobacterium tuberculosis, which causes pulmonary tuberculosis. Her research is centered on immune system cells called macrophages that are the first line of defense against airborne pathogens. They engulf the M. tuberculosis, bringing it to white blood cells called T cells, which should kill the TB germ. However, M. tuberculosis is able to take refuge in macrophages by diverting some host defense mechanisms. This hijacking of the macrophages defense system interferes with the ability of the immune system to protect people from disease. "A clear understanding of the interactions between M. tuberculosis and the immune system at the cellular level is crucial to our attempts at developing novel drug targets and vaccines," she says.

Dr. Jayaraman, who is from India, has seen the high toll TB has taken in her country. "It's a very big public health problem, and we need better treatments to control infection," she says.

With the assistance of an American Lung Association Senior Research Training Fellowship, Dr. Jayaraman is studying how recently discovered molecules called Tim3 on the surface of T-cells regulate the macrophage response to M. tuberculosis. "We see that Tim3 expression levels on T cells increase following M. tuberculosis infection, and we think it plays an important role in immunity to M. tuberculosis," she says. She is studying a novel way in which Tim3 on T-cells can activate M. tuberculosis-infected macrophages by binding to a receptor on the macrophages. This receptor sends a signal into the macrophage and activates it, allowing it to efficiently kill M. tuberculosis.

Dr. Jayaraman has been encouraged by her findings that mice infected with TB who were treated with the Tim3 protein experienced a dramatic reduction in the TB bacteria in their lungs. "Tim3 might one day become an important treatment option that we could use to reduce tuberculosis," she says.

Currently, TB is treated with a nine-month regimen of drugs. Many people don't finish the treatment, which contributes to the growing problem of drug resistance. "Medications that directly activate macrophages to kill M. tuberculosis could bypass the problem of drug resistance. Understanding how Tim3 activates macrophages to kill M. tuberculosis will lead to the development of medications that can similarly activate macrophages regardless of drug resistance," she says.

More immediately, she plans to treat mice with Tim3 before they have been infected with TB, to see if the protein can prevent the infection.

"It is a great honor to receive the American Lung Association grant," she says. "In addition to the funding, the grant acknowledges that our work is significant."