Abstract: Some scientists believe that infection may damage the intestinal nervous system, leading to irritablebowel syndrome (IBS). Researchers at Rockefeller University have uncovered the cause of intestinal neuron death and the protective mechanism of the immune system through experiments. The research results were published in Cell.
Enteric-associated neurons (EANs) are closely related to immune cells, and they monitor and regulate intestinal homeostasis at all times. In order to understand the effect of infection on the nervous system and analyze the intestinal neurons, the researchers administered Salmonella spiB to mice, which can cause food poisoning. By constructing a mouse intestinal infection model, observations showed that intestinal motility was reduced and iEAN was reduced. And other long-term gastrointestinal symptoms.
They also found that these cells expressed two genes, NLRP 6 and Caspase 11, which promote a specific inflammatory response, which in turn could lead to programmed cell death. When researchers knocked out these genes in mouse neurons, they found that the number of neurons was reduced.
Previous studies by Mucida's laboratory have shown that intestinal muscle macrophages (MMs) express anti-inflammatory genes and cooperate with neurons to move food through the digestive tract. This study further revealed that macrophages possess certain types of receptor molecules that receive stress signals released by another group of neurons after infection. Once activated, this receptor causes macrophages to produce polyamine molecules, which in turn interfere with the cell's death process.
In summary, the study found that:
(1) intestinal infection can cause neuronal reduction and long-term gastrointestinal symptoms, the former depends on the Nlrp 6 and caspase 11 genes;
(2) MMs respond quickly to intestinal pathogens;
(3) nerves Yuan's death is limited by the MM-β2-adreno-arginase 1-polyamine axis. Post-doctoral researcher Paul Muller of the research group mentioned that with the knowledge of MMs, we can think about how to reduce the inflammatory response of neurons being killed, such as by promoting the production of polyamines, diet or restoring the intestinal microbial community, etc. Develop better treatments.
Reference: Matheis F, Muller PA, Graves CL, et al. Adrenergic Signaling in Muscularis Macrophages Limits Infection-Induced Neuronal Loss. Cell. 2020;180(1):64–78.e16. doi:10.1016/j.cell.2019.12.002
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