Cell: challenge the routine! The nervous system not only detects Salmonella in the gut, but also actively resists the harmful bacteria

December 22, 2019 / Biovalley BIOON / - -- in a new study, researchers from Harvard Medical School in the United States found that the nervous system in the gut of mice not only senses the presence of Salmonella, but also actively resists the infection of this harmful bacteria by deploying two lines of defense The related research results were recently published in the Journal of cell The title of the paper is "got innovative reactor neurons regulate Peyer's patch microfold cells and SFB levels to mediate Salmonella host defense" The picture is from cc0 public domain The study offers a new perspective on the traditional view that the nervous system only serves as a watchdog, that is, to detect and alert the body to the presence of danger These results suggest that by directly interfering with the ability of Salmonella to infect the gut, the nervous system is not only a risk detector, but also a defense against risk "Our results show that the nervous system is more than just a simple sensor and alarm system," said Isaac Chiu, a neuroimmunologist and associate professor at the blavatnick Institute at Harvard Medical School We also found that nerve cells in the gut function much more than that They regulate intestinal immunity, maintain intestinal homeostasis, and actively resist infection " Specifically, these experiments have shown that pain sensing neurons embedded in the small intestine and cells on the Peyer's patch can be activated by the presence of Salmonella, which, as a food-borne bacterium, causes one quarter of bacterial diarrhea worldwide Once activated, these neurons use two defense strategies to prevent Salmonella from infecting the gut and spreading to other parts of the body First, they regulate the cellular pathways that allow microbes and substances to enter and leave the small intestine Second, they increase the number of protective intestinal bacteria called segmented figmentous bacteria (SFB), which is part of the intestinal microbiome Bacteria activate our nervous system Under normal circumstances, Peyer's aggregation lymph nodes (only the aggregation of lymphoid and immune tissues found on the wall of the small intestine) can scan the environment, sample the substances in the environment and determine which substances can enter the intestine In order to perform this function, the Peyer's aggregation lymph nodes are covered with cell channels called microfold cells (M cells), which open and close the regulative substances and microorganisms flowing into the intestine M cells are the main entry point for Salmonella and other dangerous bacteria to invade the small intestine To do this, Salmonella injects transcription factors that stimulate cells in the gut to become M cells into the gut Next, Salmonella attaches to sugar molecules on the surface of M cells and uses its antennae to open these cell channels The bacteria then wobble into the gut To understand the role of gut neurons in resistance to infection, the researchers compared the response of mice with or without them to Salmonella The gut neurons in one group of mice were intact, those in the other group of mice lost their functions or deletions by genetic means, and those in the other group of mice lost their functions by chemical means Experiments show that in the presence of Salmonella, gut neurons fight back by releasing a neurochemical called CGRP, which slows down the differentiation of M cells, thus reducing the number of entry points that Salmonella can use In addition, these experiments show that gut neurons initiate another form of defense By releasing CGRP, they enhance the presence of SFB bacteria, which, in addition to other beneficial functions, can also prevent Salmonella invasion It's not clear how they did it, but Chiu and colleagues say a reasonable mechanism might be for SFB bacteria to use their tiny hooks to attach themselves to the intestinal wall and form an exclusion coating that can prevent the pathogenic bacteria Both of these two defense mechanisms play a reliable role in mice with intact intestinal neurons However, this was not the case in mice lacking these gut neurons Indeed, gut biopsies of mice with inactivated gut neurons showed that Salmonella infiltrated their Peyer's aggregation lymph nodes at a higher rate than those with intact gut neurons These mice lacking gut neurons also had fewer protective SFB bacteria in their gut Not surprisingly, these mice were more likely to be infected with Salmonella and spread more widely than mice with intact gut neurons "It's increasingly clear that the nervous system interacts directly with infectious organisms in various ways, thereby affecting immunity," Chiu said Bacteria do activate our nervous system " These new findings are consistent with past studies by the Chiu team that have shown strong tripartite interactions between infection and the nervous and immune systems But unlike these new findings, the previous study showed that the nervous system is sometimes used by infectious microbes to serve them For example, Chiu's previous study found that when Staphylococcus aureus causes a serious lung infection, the nervous system in the lungs can change the immune response In another study, Chiu's team has found that the bacteria, which causes predatory diseases, hijack the nervous system, weakening immune and physical defenses Diverse functions these new findings further confirm that the nervous system has far more extensive functions than sending and receiving signals to the brain "Our findings reveal important interactions between the nervous system and the immune system," said Nicole Lai, lead author of the paper and Immunology researcher at Chiu laboratory It's clearly a two-way highway, and both systems send messages and interact with each other to regulate the protective response during infection " Indeed, the gut contains a lot of nerves, so it's often called the second brain As an alarm system designed to warn the body of imminent threats, the nervous system works super fast So, the researchers say, these new findings suggest that evolution has used this feature to increase protection "If you think about it, neural involvement in the immune response is an evolutionary smart way to protect the gut from infection by reusing existing functions," Chiu said The researchers say their findings may also help explain previous observations that using opioids (which silence pain sensing nerve fibers) and other neuromodulators makes people more susceptible to infection "If you turn down neural signals to relieve pain, you may inadvertently weaken their protection," he said Our observations support this view " The researchers said that the interaction between gut neurons and M cells, which play a protective role, represents an area to be further studied, because M cells are also caused by other organisms (including E.coli, Shigella, Yersinia) that cause serious human diseases, as well as prions and self-proliferation, which can cause rare but generally fatal neurodegeneration Disease of misfolded protein masses used These results also point to potential therapeutic approaches involving the regulation of neural signals to enhance intestinal immunity or inflammation "The idea is that if we can somehow stimulate these protective gut neurons or mimic their activity, then we can activate the immune response and enhance the body's resistance to infection," Chiu said (BIOON Com) reference: 1 Nicole y Lai et al Gut innovative nociceptor neurons regulate Peyer's patch microfold cells and SFB levels to mediate Salmonella host defense Cell, 2019, DOI: 10.1016/j.cell.2019.11.014 2 Nervous system doesn't merge detect presence of Salmonella, it actively defends body against it: study https://medicalxpress.com/news/2019-12-nervous-doesnt-presence-salmonella-defends.html