Research
Immune System Disease
Fighting Ability
Emory Researchers Discover Novel Mechanism Of How Anthrax
Impairs Immunity
7-17-2003
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.
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"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.
This story has
been adapted from a news release issued by Emory University Health
Sciences Center, www.emory.edu.
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