After food poisoning, who is quietly helping you fight off bacterial infections?

Click on the blue word above to pay attention to us! Author: Romana R. Gerner & amp; Manuela raffatellu mammalian gut must be able to withstand various infectious agents.neurons have never been considered as the first line of defense against infection in the past, but recent research shows that they can help maintain the intestinal barrier function and prevent the spread of bacteria to other organs.it is generally believed that the identification and neutralization of harmful bacteria in the intestinal tract are accomplished by epithelial cells and immune cells.however, the article published in cell by Lai et al. [1] of Harvard Medical School found that some intestinal neurons also played an unexpected key role in anti infection.the gut is exposed to a variety of foods, antigens (molecules that trigger immune responses when identified as "alien"), usually harmless symbiotic microorganisms, and harmful microorganisms (pathogens).therefore, it is difficult for intestinal cells to judge enemy and friendly forces.epithelial cells and immune cells cooperate to adjust this fine balance, which can not only maintain the immune tolerance of human body to food antigens and intestinal symbionts, but also initiate protective immune response to remove pathogens in time.intestinal nerve cells (including the intestinal nervous system) can sense molecules derived from microorganisms and promote the defense response to microorganisms by interacting with epithelial cells and immune cells [2].the human intestinal nervous system contains about 108 neurons. This complex network is crucial for the regulation of many intestinal functions, such as blood flow and intestinal content movement [3].in addition, some nerve cells can play a close role in the composition of intestinal immune system, and even regulate it [4].among these neurons, there is a class of neurons called pain receptors.these receptors can cause pain or discomfort when they feel potentially harmful stimuli, such as extreme cold and heat, reactive chemicals, and mechanical injury [5].they can also directly detect pathogens and their related molecules, and cause pain during infection [6].however, it has not been clear whether pain receptors directly help to prevent bacteria from invading host tissues.Salmonella is a common pathogen causing food poisoning.Salmonella can cause many diseases, ranging from infectious diarrhea (gastroenteritis) to spreading from the intestine to other parts, causing life-threatening complications [7,8].one of the main sites of Salmonella invasion into the intestine is the dome shaped follicles called Peyer's patches (Fig. 1).as a key sensor for intestinal mobilization of immune defense, these lymphoid follicles monitor and respond to intestinal pathogens and symbionts through immune cells and special epithelial cells called M cells.M cells take antigen from intestinal cavity and pass it to lower immune cells [9]. Immune cells decide whether to initiate protective immune response or maintain antigen tolerance according to antigen type.Figure 1 | mammalian gut neurons help protect against bacterial infections.Lai et al. [1] reported that a group of intestinal neurons called pain receptors expressed TRPV1 and Nav1.8 proteins, which could resist Salmonella infection in mice.A, Salmonella leaves the intestinal cavity and enters M cells (special epithelial cells in the area of Pyle's collecting lymph nodes), invades intestinal tissues, and then spreads to other organs.SFB is a kind of intestinal symbiotic bacteria, which can combine with M cells or other intestinal epithelial cells, and has the ability to control Salmonella infection [13].b, the authors report that these pain receptors coordinate the defense response against Salmonella infection, mainly manifested by a decrease in the number of M cells and an increase in intestinal SFB colonization.these changes were associated with Salmonella infection and reduced extraintestinal spread.Lai et al. Also pointed out that pain receptors mainly rely on the secretion of neuropeptide CGRP to regulate the number of M cells and SFB level.although Peyer's collecting lymph nodes play an important role in the monitoring of intestinal contents, some pathogens, such as Salmonella, norovirus (a common culprit of gastroenteritis) and prions (infectious pathogenic protein), may use M cells to invade intestinal tissue [10,11].it is worth noting that although the Peyer's collecting lymph nodes are physically adjacent to intestinal neurons (including pain receptors), their functional connections have not been clear in the past.Lai et al. Used a mouse model to evaluate the role of pain receptors in resisting Salmonella typhimurium infection.according to the research report, some intestinal pain receptors (especially those that express ion channel proteins TRPV1 and Nav1.8) can protect the intestine from the invasion of Salmonella, thus preventing the spread of Salmonella to liver, spleen and other organs.interestingly, the authors found that the protective effect of pain receptors is not mediated by well-known antimicrobial defense mechanisms, such as activating immune cells or changing the level of antimicrobial peptides produced by intestinal cells.in fact, pain receptors reduce the number of M cells during Salmonella infection.as M cells are the main entry point of Salmonella, the area of Salmonella invasion may also decrease once the number of M cells decreases. the researchers used genetic engineering technology to make the intestinal pain receptors of mice unable to express TRPV1 or Nav1.8 channel proteins, and analyzed the composition of intestinal flora in mice without Salmonella infection. compared with normal mice, the levels of SFB in the intestines of mice lacking TRPV1 or Nav1.8 channel protein were significantly decreased. segmented filamentous bacteria are a kind of intestinal symbiotic bacteria attached to intestinal epithelial cells, especially M cells [12], which is crucial for intestinal colonization against pathogens (including Salmonella). Lai and his colleagues studied whether there was a relationship between the decreased number of M cells and the degree of SFB colonization in Peyer's collecting lymph nodes. the results showed that both pain receptor mediated and antibody based stimulation could increase SFB colonization, indicating that the number of M cells can regulate intestinal SFB colonization (but the exact mechanism has not been fully clarified). this change is beneficial because it limits the infection of Salmonella. The reason may be that the increase of SFB colonization and the decrease of M cell number lead to the decrease of available invasion sites of Salmonella. finally, Lai et al. Also proposed that when the pain receptor expressing TRPV1 was stimulated by Salmonella, a neuropeptide called CGRP was released. this small molecule is the intercellular communication molecule. CGRP can directly regulate the number and function of M cells, as well as SFB level in the intestine. this study revealed for the first time the role of intestinal pain receptors in host resistance to Salmonella infection. this important discovery reveals the complex interaction between mammalian intestinal epithelial cells, neurons and intestinal microorganisms, and deepens our understanding of intestinal immunity. whether the immune response mediated by pain receptors can also resist other pathogenic microorganisms remains to be determined. however, it has been reported that pain receptors have a protective effect on Citrobacter infection in mice [14]. one of the key research directions in the future is to clarify whether the findings of Lai and colleagues are related to human health. for example, to explore whether long-term use of opioid analgesics (such as morphine) will affect the pain receptor mediated antibacterial effect. this problem is worth studying because pain receptors happen to be the main target of opioid drugs, and the feeding of morphine to mice will change their intestinal microbial composition [15,16]. Br / > in addition, the use of morphine in some parts of the gut may promote the spread of Gram-negative bacteria to the human body. further exploration of the interaction between gut neurons and immune cells in the process of infection may lead to exciting new discoveries and refresh our understanding of host defense. < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / < br / References: 1.lai, N.Y. y. et al. Cell: 180, 33 – 49 (2020), 2.yoo, B, B. B. & amp; Mazmanian, S., Mazmanian, S.K. K. immunity, 910 – 926 (2017), 910 – 926 (2017), 3.kulkarni, S., S.et Al, J. neurosci.38, 9346 – 9346 – 9346 – 9354 (. 5. Julius, D. & amp; BASBAUM, A. I. Nature 413, 203–210 (2001).6.Baral, P., Udit, S. & Chiu, I. M. Nature Rev. Immunol. 19, 433–447 (2019).7.Majowicz, S. E. et al. Clin. Infect. Dis. 50, 882–889 (2010).8.Gordon, M. A. J. Infect. 56, 413–422 (2008).9.Mabbott, N. A., Donaldson, D. S., Ohno, H., Williams, I. R. & Mahajan, A. Mucosal Immunol. 6, 666–677 (2013).10.Jung, C., Hugot, J.-P. & Barreau, F. Int. J. Inflam. 2010, 823710 (2010).11.Chiocchetti, R. et al. Cell Tissue Res. 332, 185–194 (2008).12.Meyerholz, D. K., Stabel, T. J. & Cheville, N. F. Infect. Immun. 70, 3277–3280 (2002).13.Garland, C. D., Lee, A. & Dickson, M. R. Microb. Ecol. 8, 181–190 (1982).14.Ramirez, V. T. et al. J. Infect. Dis.  (2020).15.Wang, F. et al. Sci. Rep. 8, 3596 (2018).16.Hilburger, M. E. et al. J. Infect. Dis. 176, 183 – 188 (1997). The original article was published in the news and opinion section of nature on April 20, 2020 under the title of "gut pain sensors help to combat effect" ("nature")| doi:10.1038/d41586-020-01105-1