July 2, 2012 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.
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- 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
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