What is already known
Gut inflammation alters the balance and function of gut microbes, but how the body senses and reacts to these microbiota changes is not yet fully understood. Mucosal-associated invariant T cells, or MAIT cells, are a type of immune cells found in the liver and gut that are activated in conditions associated with gut dysbiosis, such as inflammatory bowel disease and colorectal cancer.
What this research adds
Working in mice, researchers found that MAIT cells detect specific metabolites produced by bacteria. In an inflamed gut, microbes expand their production of riboflavin, which leads to an increase in riboflavin-derived metabolites. These metabolites activate MAIT cells, leading to anti-inflammatory responses. Mice lacking MAIT cells were more susceptible to gut inflammation and colorectal cancer.
Conclusions
The findings indicate that MAIT cells act as detectors of gut inflammation by interacting with the microbiota.
Gut inflammation alters the balance and function of gut microbes, but how the body senses and reacts to these microbiota changes is not yet fully understood. Now, working in mice, researchers have found that a specific type of immune cells called MAIT cells can detect molecules produced by microbes during intestinal inflammation. The resulting immune activation leads to anti-inflammatory responses in the gut.
The findings, published in Science Immunology, indicate that MAIT cells act as detectors of gut inflammation by interacting with the microbiota.
MAIT cells, or mucosal-associated invariant T cells, are a type of immune cells found in the liver and gut that are activated in conditions associated with gut dysbiosis, such as inflammatory bowel disease and colorectal cancer. However, how these cells interact with the microbiota is largely unknown.
So, researchers led by Yara El Morr at the Institut Curie in Paris set out to investigate the role of MAIT cells during gut inflammation in mice.
Activating immune responses
The researchers found that molecules able to activate MAIT cells, called MAIT ligands, are mostly produced by gut microbes such as Proteobacteria and Deferribacteres, which are adept at surviving in oxygen-rich environments. These bacteria bloom in the gut lumen during inflammation, the team also found.
In mice, gut inflammation brought immune cells into the gut lumen and increased the expression of genes linked to antibacterial defenses and riboflavin synthesis. In particular, the researchers found that Mucispirillum schaedleri is a major producer of MAIT ligands.
MAIT ligands produced in the gut quickly diffused through the gut wall to the lymph nodes and liver. Gut inflammation also increased the number of MAIT cells in the colon, leading to anti-inflammatory responses in the gut. Mice lacking MAIT cells were more susceptible to gut inflammation and colorectal cancer, the researchers found.
Gut surveillance
The results suggest that MAIT cells serve a surveillance role in the gut, the authors say. People with inflammatory bowel disease show activated MAIT cells that are recruited to inflamed sites and are linked with disease activity.
Other studies have shown that MAIT cells reduce gut damage and inflammation-associated tumors, promoting the integrity of the gut barrier. The current findings indicate that these cells play an important role in reducing gut inflammation and promoting tissue repair.
“We highlight a specific function of MAIT cells in the colon: monitoring the activity of a microbial metabolic pathway indicative of intestinal inflammation to provide anti-inflammatory and tissue-repair mediators in return,” the authors say.
