Sometimes the end of an intestinal infection is just the beginning of more misery. Of those who contract traveler's diarrhea, for example, an unlucky few go on to develop irritable bowel syndrome (IBS), a chronic inflammation of the intestinal tract.
Scientists aren't sure exactly how this happens, but some think an infection may contribute to IBS by damaging the gut nervous system. A new Rockefeller study takes a close look at why neurons in the gut die and how the immune system normally protects them.
Conducted with mice, the experiments described recently in Cell offer insight on IBS and could point toward potential new treatment approaches. Keeping inflammation in check
In a healthy gut, the immune system must strike a careful balance between responding to threats and keeping that response in check to avoid damage.
Inflammation helps the gut ward off an infection, but too much of it can cause lasting harm. Our work explores the complex mechanisms that prevent inflammatory responses from destroying neurons." Daniel Mucida, associate professor and head of the Laboratory of Mucosal Immunology
To understand the effects of an infection on the nervous system, Mucida and his colleagues gave mice a weakened form of Salmonella , a bacterium that causes food poisoning, and analyzed neurons within the intestine. They found that infection induced a long-lasting reduction of neurons, an effect they attributed to the fact these cells express two genes, Nlrp6 and Caspase 11 , which can contribute to a specific type of inflammatory response.
This response, in turn, can ultimately prompt the cells to undergo a form of programmed cell death. When the researchers manipulated mice to eliminate these genes specifically in neurons, they saw a decrease in the number of neurons expiring.
"This mechanism of cell death has been documented in other types of cells, but never before in neurons," says Fanny Matheis, a graduate student in the lab. "We believe these gut neurons may be the only ones to die this way." Macrophages to the rescue
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