Seattle BioMed discovers new knowledge about immune response to tuberculosis
Discovery helps researchers advance future TB vaccine design
As the world raises awareness of the global tuberculosis burden on World TB Day — March 24, 2012 — Seattle Biomedical Research Institute (Seattle BioMed) is celebrating an important discovery that could direct new strategies for TB vaccine development. Known as “the world’s most successful disease,” TB remains the second deadliest infectious disease, killing more than one million people annually. However, by studying the basic biology of M tuberculosis (the bacteria that causes TB disease), as well as its interaction with the immune system, Seattle BioMed researchers have grasped an important piece of new information about TB’s ability to manipulate immune response.
In a recent study that was inspired by a National Institutes of Health investigation of immune response to leishmaniasis — another deadly infectious disease — Seattle BioMed Principal Investigator Kevin Urdahl, M.D., Ph.D., and Shahin Shafiani, Ph.D., led an investigation into the methods by which TB manipulates the immune system to react in slow motion, enabling the deadly microbes to make themselves at home in the lung and advance disease progression before immune cells can properly combat the infection. “If we don’t understand TB’s tricks, we can’t develop strategies to get around them,” said Urdahl. “So, my lab set out to investigate the methods by which TB is able to orchestrate this grand slowdown,” he said.
Scientists have long known that by the time immune cells respond to TB infection, it is often too late to provide much benefit to the patient. TB has found a way to replicate unchecked within the body’s own cells, for far too long, thus achieving a higher level of infection that can lead to more serious symptoms for the patient. Urdahl’s lab hypothesized that, similar to the findings of the leishmaniasis study, specialized immune cells called regulatory T cells (T reg cells) may be responsible for the significant delay in immune response to TB. “Normally, T reg cells function to prevent other protective T cells from mounting too potent an attack on the body’s tissue, which could lead to autoimmune diseases,” Urdahl explained. “But in the case of TB infection, the bacteria may have evolved to trigger a specific subset of T reg cells that can recognize TB antigens and trigger a suppressive cell response before the protective T cells have a chance to react.”
Shafiani tested and confirmed their hypothesis: Only the T reg cells that recognized TB antigens could proliferate and be activated during TB infection. These findings suggest that the expansion of antigen-specific T reg cells occurs only in a subset of infections, such as leishmaniasis and TB. “We believe that the expression of these specialized T reg cells is directed by the pathogen itself to create an environment that supports the pathogen’s growth and survival,” said Urdahl.
Urdahl and his lab hope to apply this new information to better TB vaccine development. “We know that T cells are absolutely essential for protection against TB, but with this new knowledge about antigen-specific T reg cells, we now know it is also essential to look at the ratio of protective T cells to suppressive T cells specific for TB antigens,” he said. “With enough knowledge, we should be able to outsmart TB.”
Scientists at Seattle BioMed believe that a solid understanding of the immune response to TB and the basic biology of the microbe are critical to developing a new vaccine or to improving current therapies. While the Urdahl lab’s discovery presents just one piece of the puzzle, it’s a significant step toward better understanding this disease that has mystified scientists for centuries.
ABOUT SEATTLE BIOMEDICAL RESEARCH INSTITUTE:
Seattle BioMed is the largest independent, non-profit organization in the U.S. focused solely on infectious disease research. Our research is the foundation for new drugs, vaccines and diagnostics that benefit those who need our help most: the 14 million who will otherwise die each year from infectious diseases, including malaria, HIV/AIDS and tuberculosis. Founded in 1976, Seattle BioMed has nearly 400 staff members. By partnering with key collaborators around the globe, we ensure that our discoveries will save lives sooner. For more information, visit www.seattlebiomed.org.
