The Effect of a STING
For the second year in a row, Glen N. Barber, Ph.D., professor of medicine and Eugenia J. Dodson Chair in Cancer Research, and Hiroki Ishikawa, Ph.D., a post-doctoral fellow, have earned recognition for their research findings about the immune system with an article in the prestigious journal Nature. Their latest findings were published in the October 2009 issue. In the September 2008 issue of Nature, Barber and Ishikawa reported their seminal discovery of a molecule, STING (STimulator of INterferon Genes), which activates the body’s innate immune system by triggering the production of interferon. That study focused on fibroblast cells, the most common cells, in vitro.
The research team’s latest work takes the STING discovery a step further, examining how the molecule affects more specific cell types. Barber and Ishikawa included macrophages and dendritic cells, which activate anti-pathogen B and T cell responses. They also evaluated the importance of STING in an animal model and found that it’s a “vital element,” says Barber.
After discovering that STING initiates a sequence of events that unleashes interferon against viruses, Barber and Ishikawa wanted to take a closer look at the molecule’s role in attacking DNA pathogens such as herpes simplex virus and the bacteria Listeria, among others. Mice that were lacking STING were found to be extremely sensitive to virus infection. Barber declares that “STING is absolutely essential to the body’s defense against a variety of different DNA and even RNA pathogen types.”
This finding might help other scientists gauge the immune system’s reaction to plasmid DNA-based vaccines, such as those being developed to combat flu. Vaccines are designed to trigger the body to make antiviral or anti-bacterial antibodies and T cells. Barber believes the human innate immune system will react in the same way as animal models in the laboratory. Without STING, a DNA-based vaccine won’t be effective, because the body will not create interferon and other cytokines essential for stimu-lating an adaptive immune response.
This NIH-funded study by Barber and Ishikawa further solidifies the importance of STING’s role in activating the pathway to begin production of interferon. Next the research team plans to examine STING’s effect on parasites and explore how the molecule regulates T-cell response to DNA-based vaccines. Barber hopes a deeper understanding of this connection will lead to “improved and safer vaccines to fight cancer and other serious illnesses.”
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