ARTICLE
New research by scientists at Harvard Medical School has found that nerves in the guts of mice do not merely sense the presence of Salmonella but actively protect against infection by this dangerous bacterium by deploying two lines of defense. The new findings add to a growing body of knowledge showing that the nervous system has a repertoire far broader than signaling to and from the brain. The study casts in a new light the classic view of the nervous system as a mere watchdog that spots danger and alerts the body to its presence. The results show that by directly interfering with Salmonella's ability to infect the intestines, the nervous system is both a detector of danger and a defender against it. "Our results show the nervous system is not just a simple sensor-and-alert system," said the study's lead investigator at Harvard Medical School. "We have found that nerve cells in the gut go above and beyond. They regulate gut immunity, maintain gut homeostasis and provide active protection against infection.” Specifically, the experiments reveal that pain-sensing neurons embedded in the small intestine and beneath cells called Peyer's patches are activated by the presence of Salmonella, a foodborne bacterium responsible for a quarter of all bacterial diarrheal disease worldwide. Once activated, the nerves use two defensive tactics to prevent the bug from infecting the intestine and spreading throughout the rest of the body. First, they regulate the cellular gates that allow microorganisms and various substances to go in and out of the small intestine. Second, they boost the number of protective gut microbes called SFB (segmented filamentous bacteria), which are part of the microbiome in the small intestine. Under normal conditions, Peyer's patches -- clusters of lymphatic and immune tissue found exclusively on the wall of the small intestine -- scan the environment, sample substances and determine what can go into the intestine. To perform this function, Peyer's patches are studded with microfold cells, or M cells, which are cellular channels that open and close to regulate influx of substances and microorganisms into the intestine. M cells are the major entry points that Salmonella and other dangerous bacteria exploit to invade the small intestine. To do so, the Salmonella bacterium injects into the gut transcription factors that stimulate intestinal cells to become M cells. Next, Salmonella latches onto sugars sitting atop the M cells -- the cellular gates -- and uses its tentacles to prop the gates open. The bacterium then wiggles its way into the intestine. Experiments showed that in the presence of Salmonella, gut neurons fire back by releasing a neurochemical which slows down M cell differentiation, thereby reducing the number of entry points that Salmonella can use. Additionally, the experiments show, gut neurons launch another form of defense. They boost the presence of SFB microbes -- microorganisms that, among performing other beneficial functions, also guard against Salmonella invasion. "It is becoming increasingly clear that the nervous system interacts directly with infectious organisms in various ways to affect immunity,” the researcher said. "Bacteria literally do get on our nerves.” The findings are in line with past research by the Harvard Medical group showing a powerful three-way interplay between infection and the nervous and the immune systems. But in contrast to the new findings, the previous work showed that the nervous system can, at times, be exploited by infectious organisms to their advantage. For example, previous research found that nerves in the lungs can alter immune response in serious lung infections with the bacterium Staphylococcus aureus, commonly known as staph. In another study, the team discovered that the bacterium that can cause flesh-eating disease hijacks nerves as a way to dampen immune defenses and weaken the body's defenses. "Our findings illustrate an important cross talk between the nervous system and the immune system," said study first author. "It is clearly a bidirectional highway with both systems sending messages and influencing each other to regulate protective responses during infection.” Indeed, the gut contains so many nerves that it has often been called the second brain. As an alert system designed to warn the body of looming threats, the nervous system acts ultrafast. The researchers say their findings could also help explain previous observations showing that the use of opioids -- which silence pain-sensing nerve fibers -- and other nerve-modulating drugs can make people more prone to infections. "If you dial down nerve signaling in an effort to reduce pain, you may be inadvertently also dampening their protective abilities." Source: https://www.sciencedaily.com/releases/2019/12/191205141739.htm