Public release date: 2-Oct-2008
NIH/National Institute of Allergy and Infectious Diseases
DNA of good bacteria drives intestinal response to infection
A new study shows that the DNA of so-called "good bacteria" that
normally live in the intestines may help defend the body against
infection.
The findings, available Oct. 2 online in the journal Immunity, are
re****ted by Yasmine Belkaid, Ph.D., and her colleagues in the Laboratory
of Parasitic Diseases at the National Institute of Allergy and
Infectious Diseases (NIAID), part of the National Institutes of Health.
A person normally has 300 to 500 species of beneficial bacteria, known
as commensals, in their intestines. These bacteria are not harmful and,
in fact, help an individual maintain his or her digestive health.
Typically, the immune system does not attack gut commensals, even though
they are bacteria.
"Within the body of a healthy adult, microbial cells vastly outnumber
human cells. Research to understand these microbial communities is an
exciting scientific frontier," says Anthony S. Fauci, MD, NIAID
director. "Among many op****tunities related to the so-called
'microbiome,' targeting beneficial bacteria may offer new avenues for
therapy against infectious and immune-mediated diseases."
Just how commensals protect against harmful bacteria, known as
pathogens, is a complex question. "Pathogens often behave similarly to
gut commensals," Dr. Belkaid says. Because the body needs commensals but
also has to rid itself of disease-causing microbes, the immune system
must distinguish the good bugs from the bad ones.
One mechanism of protection is through the interaction between the
commensals and certain immune cells in the intestines. This interaction
occurs through the binding of the commensals to receptors on the T cells
known as Toll-like receptors (TLRs).
In healthy individuals, some intestinal T cells (known as Tregs) play a
regulatory role, recognizing commensals and keeping the immune system
from attacking them. During an infection, however, T cells ****ft into
attack mode to fight the infection. The factors controlling this ****ft
from defense to offense have not been well understood.
Dr. Belkaid's team describes a novel way in which the Tregs are
regulated to facilitate an immune response to a pathogen. They found
that during an infection, the DNA of the body's beneficial bacteria
binds to a specific receptor on the intestinal immune cells, called
TLR9. The binding of commensal DNA to TLR9 in the presence of a pathogen
prevents the generation of Tregs in favor of the generation of
protective T cells. These protective T cells can then clear the body of
the invading pathogen.
In effect, the commensal DNA acts as a natural adjuvant by boosting the
activity of T cells so they can destroy the invading pathogen.
"There is a balance of regulatory immune signals in the body," notes Dr.
Belkaid. "During an infection, we've found that commensals can break
this balance in favor of an infection-fighting response."
While the immune system must react to invading pathogens to maintain
health, an immune response to commensals can cause problems. For
example, certain inflammatory bowel diseases, such as Crohn's disease,
are thought to be caused in part by immune reactions against commensal
bacteria.
Understanding how commensals interact with the immune system opens up
the possibility of using beneficial bacteria as targets for future oral
therapies against infections or autoimmune diseases
<http://www.eurekalert.org/pub_releases/2008-10/nioa-dog100208.php>
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