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Emory researchers discover novel mechanism of how anthrax impairs immunity

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 d
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Contact: Lisa Newbern
lmnewbe@emory.edu
404-727-7709
Emory University Health Sciences Center
16-Jul-2003


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