Cell: revealing the mechanism of intestinal myometrial macrophages limiting neuronal death induced by intestinal infection

January 26, 2020 / BIOON / - -- sometimes, the end of intestinal infection is just the beginning of more pain For example, among those with traveler's diarrhea, a small number of unfortunate people suffer from a chronic inflammation of the intestine called irritable bowel syndrome (IBS) Scientists are not sure how the disease occurs, but some believe that intestinal infection may cause irritable bowel syndrome by damaging the gut nervous system In a new study, researchers from Rockefeller University in the United States studied how neurons in the gut die and how the immune system usually protects them The study, based on mice, provides new insights into irritable bowel syndrome and may help people develop new treatments The related research results were recently published in the journal Cell, and the title of the paper was "adaptive signaling in muscularis macrophases limits infection induced neurological loss" Picture from cell, 2020, DOI: 10.1016/j.cell.2019.12.002 To control inflammation in a healthy gut, the immune system must maintain a careful balance between responding to threats and controlling inflammation to avoid damage Daniel mucida, co-author of the paper and director of the mucosal immunology laboratory at Rockefeller University, said: "inflammation helps the gut fight infection, but too much inflammation can cause sustained damage Our study explored the complex mechanisms that prevent inflammation from damaging neurons " To understand the effects of intestinal infection on the nervous system, mucida and his colleagues provided mice with a weakened Salmonella, a food poisoning causing bacterium, and analyzed the neurons in the gut They found that the bacterial infection caused a sustained decrease in neurons, which is due to the expression of two genes, nlrp6 and caspase 11, leading to specific types of inflammatory response This inflammatory response can eventually cause these neurons to undergo some form of programmed cell death When the researchers manipulated the mice to specifically eliminate the two genes in the neurons, they found that the number of dead neurons decreased "This mechanism of cell death has been documented in other types of cells, but has never been found in neurons before," said Fanny Matheis, a graduate student at the mucida lab who co authored the paper We think these gut neurons may be the only neurons that die in this way " Macrophage rescue is not clear how inflammation causes neuronal suicide, but these researchers have clues that it is possible to interfere with this process The key to this may be a specific set of intestinal immune cells called muscularis macrophages Previous studies in the mucida lab have shown that these cells express anti-inflammatory genes and work in concert with neurons to keep food flowing in the digestive tract If these neurons die in an infection, one possible result is constipation - one of the many uncomfortable symptoms of irritable bowel syndrome In a recent report, they showed how macrophages help neurons during infection, thereby improving this aspect of the disease Their experiments show that macrophages have some type of receptor molecules, so they can receive the stress signals released by another group of neurons in response to infection Once activated, the receptor causes macrophages to produce molecules called polyamines, which they believe may interfere with the process of cell death Returning to normal in other experiments, the researchers found that Salmonella infection alters the microbial community in the gut of mice, and when they return the intestinal flora of these mice to normal, the neurons return to normal "By using our knowledge of macrophages, people may think about ways to interfere with this inflammatory process that kills neurons," said Paul Muller, a postdoctoral researcher at the mucida lab and co lead author of the paper For example, people may develop better treatments for patients with irritable bowel syndrome by increasing the amount of polyamines in their diet or by restoring the intestinal microbiota Given that short-term stress seems to have protective effects, Muller believes that targeting short-term stress may also help (BIOON Com) reference: 1 Fanny Matheis et al, adaptive signaling in muscularis macrophases limits infection induced neurological loss, Cell (2020) DOI: 10.1016/j.cell.2019.12.002 2.Scientists examine how a gut infection may produce chronic symptoms https://medicalxpress.com/news/2020-01-scientists-gut-infection-chronic-symptoms.html