DNA of Good Bacteria Drives Intestinal Response
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 October 2 online in the journal Immunity, are reported 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 opportunities 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, Tregs shift into attack mode to fight the infection. The factors controlling this shift 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.
NIAID conducts and supports research — at NIH, throughout the United States,
and worldwide — to study the causes of infectious and immune-mediated diseases,
and to develop better means of preventing, diagnosing and treating these illnesses.
News releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at http://www.niaid.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
JA Hall et al. Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity. DOI 10.1016/j.immuni.2008.08.009 (2008).