Signals from natural intestinal bacteria are necessary for an effective
immune response to various viral or bacterial germs. This was the result
of experiments by a research team led by Prof. Dr. Andreas Diefenbach
and Stephanie Ganal at the Institute of Medical Microbiology and Hygiene
of the Freiburg University Medical Center.
The study was published in the current online edition of the Cell Press journal Immunity.
Trillions of bacteria reside in the intestines of healthy humans as
well as those of many animals. This natural intestinal flora contributes
to digestion and the metabolism of vitamins and is of critical
importance for the host organism. Recent research has shown that the
intestinal flora also plays an important role in the formation of the
immune system in the intestines and that changes to it can increase the
risk of food allergies or chronic inflammatory intestinal diseases. "It
was previously unclear to what extent the intestinal flora also
influences immunological processes outside of the intestines, such as
the defense against viral germs like the flu virus, and that was the
main question of our work," explain the scientists.
The research team infected two groups of mice with various viral
germs. One group had a normal intestinal flora and the other consisted
of so-called axenic mice, which do not have any intestinal flora due to
having been treated with antibiotics or bred under particularly clean
conditions. The immune response in the axenic mice was greatly reduced
and led the disease to take a more severe course than in the healthy
mice. When the scientists artificially provided the axenic mice with a
healthy intestinal flora, their immune response improved.
Diefenbach's group succeeded in localizing the defect in axenic mice
on the molecular level. The problem was that these mice were not
producing any soluble inflammatory mediators, so-called type I
interferons, after viral infections. Dendritic cells, i.e., cells of the
innate immune defense, react to an infection by rapidly producing these
mediators. If they are not present, the body will not be in the
position to develop a sufficient immune defense against the germs. The
team succeeded in demonstrating that signals from the intestinal
bacteria lead to a conditioning of the dendritic cells. This
conditioning takes place on the level of the DNA in the nucleus and
enables genes that encode these soluble mediators to be read better. The
scientists speak of epigenetic changes. "This is the first time anyone
has shown that changes in the natural intestinal flora resulting from
antibiotics, hygiene, or lifestyle can have substantial consequences for
the entire immune system," says Diefenbach.
Journal Reference:
- Stephanie C. Ganal, Stephanie L. Sanos, Carsten Kallfass, Karin Oberle, Caroline Johner, Carsten Kirschning, Stefan Lienenklaus, Siegfried Weiss, Peter Staeheli, Peter Aichele, Andreas Diefenbach. Priming of Natural Killer Cells by Nonmucosal Mononuclear Phagocytes Requires Instructive Signals from Commensal Microbiota. Immunity, 2012; DOI: 10.1016/j.immuni.2012.05.020
Courtesy: ScienceDaily
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