Neurons say relax: This three-dimensional view of part of a mouse intestine shows the neurons that surround tissue-protective immune cells. These neurons release norepinephrine, which instructs the immune cells to activate an anti-inflammatory response.
The immune system must protect against potential infections, but over-vigilant reactions can cause problems. New research shows neurons in the intestine send signals to immune cells to curb inflammation. This could have Rx implications for gastrointestinal diseases such as IBS.
Lamina propria macrophages are found very close to the lining of the intestinal tube, while muscularis macrophages are in a deeper tissue layer, more distant from what passes through the intestine. Using an imaging technique developed by Marc Tessier-Lavigne’s Lab of Brain Development and Repair that allows scientists to view cellular structures in 3D, the researchers looked in depth at the differences between the two populations. In addition to variations in how the cells look and move, they noticed that intestinal neurons are surrounded by macrophages.
Highlights •Gut lamina propria and muscularis macrophages show unique intra-tissue adaptation •Muscularis macrophages express a tissue-protective gene profile •Gut extrinsic sympathetic innervation is activated upon distal bacterial infection •β2 adrenergic receptor signaling mediates MM polarization upon bacterial infection
They found lLP macrophages preferentially express pro-inflammatory genes. In contrast, the muscularis macrophages preferentially express anti-inflammatory genes, and these are boosted when intestinal infections occur. “We wanted to know where this signal was coming from that induced this different response to infection,” says Mucida. “We came to the conclusion that one of the main signals seems to come from neurons, which appear in our imaging to almost be hugged by the muscularis macrophages.”
In other experiments, they found muscularis macrophages carry receptors on their surface that allow them to respond to norepinephrine produced by neurons. The researchers also observed that the muscularis macrophages are activated within 1-2 hours following an infection–significantly faster than a response would take if it were completely immunological, not mediated by neurons. They believe that was because these deeply embedded macrophages receive signals from neurons, they are able to respond rapidly to an infection, even though they are not in direct contact with the pathogen.
“We now have a much better picture of how the communication between neurons and macrophages in the intestine helps to prevent potential damage from inflammation,” says Mucida. “It’s plausible that a severe infection could disrupt this pathway, leading to the tissue damage and permanent gastrointestinal changes that are seen in diseases like irritable bowel syndrome. These findings could be harnessed in the future to develop treatments for such diseases.” http://newswire.rockefeller.edu/2016/01/22/the-neurons-in-our-gut-help-the-immune-system-keep-inflammation-in-check/
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