July 17, 2003 ATLANTA – In the first study of its kind, researchers led by Bali Pulendran, PhD, at the Emory Vaccine Center and the Yerkes National Primate Research Center have shown that anthrax lethal factor (LF) impairs the function of dendritic cells and thereby compromises the immune system's ability to fight the microbe. The findings, which appear in the July 17 issue of Nature, have implications for developing more effective anthrax therapies and guiding researchers in better controlling detrimental immune responses, such as in autoimmune diseases and organ rejection following transplant surgeries.
For his study, Dr. Pulendran, associate professor in the Department of Pathology and Laboratory Medicine at Emory University School of Medicine, and Anshu Agrawal, PhD, a post-doctoral fellow in his lab, in collaboration with Conrad Quinn, PhD, and Jai Lingappa, MD, at the Centers for Disease Control and Prevention, and Steve Leppla, PhD, at the National Institutes of Health, chose to study dendritic cells versus the previously studied macrophages. Dendritic cells are widely recognized as the most efficient antigen-presenting cells, making them pivotal in initiating and modulating any immune response against microbes.
"This is the first study that demonstrates any interaction between Bacillus anthracis and dendritic cells, " says Dr. Pulendran. "Our findings reveal a novel mechanism of action by which the microbe targets the host-immune reaction."
In the study, Dr. Pulendran's research team demonstrated that LF impairs dendritic cell function by disrupting the mitogen-activated protein (MAP) kinase enzymes within dendritic cells. Consequently, the dendritic cells become lethargic and unable to act normally, thereby preventing the activation of the immune system to attack microbes such as anthrax.
"When a person is infected with a microbe, we count on the immune system to begin fighting the foreign substance immediately," Dr. Pulendran commented. "When the dendritic cells are compromised, such as in our study with the anthrax lethal factor, the innate immune system is unable to stimulate the immune response, thus permitting the microbe to spread unchecked. Our ultimate goal is to apply this novel finding to develop better anthrax treatments and to shape future research into controlling immune responses more appropriately," Dr. Pulendran continued.
The Emory researchers' immediate next steps are to test the effects of LF in suppressing other immune models, such as in allergies and autoimmune diseases, and to look more closely at immune responses several days post infection, when toxic-shock-like symptoms begin.
The mission of the Emory Vaccine Center is to create new technologies for the prevention of emerging infectious diseases, by conducting basic and translational research and clinical trials. The Vaccine Center was established in 1996 with support from Emory University and the Georgia Research Alliance.
The Yerkes National Primate Research Center of Emory University is one of eight National Primate Research Centers funded by the National Institutes of Health. The Yerkes Center is a multidisciplinary research institute recognized as a leader in biomedical and behavioral studies with nonhuman primates. Yerkes scientists are on the forefront of developing vaccines for AIDS and malaria, and treatments for cocaine addiction and Parkinson's disease. Other research programs include cognitive development and decline, childhood visual defects, organ transplantation, the behavioral effects of hormone replacement therapy and social behaviors of primates. Leading researchers located worldwide seek to collaborate with Yerkes scientists.
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