Jackson Labs ME/CFS Collaborative Center Director Derya Unutmaz and his collaborator and microbiome expert Julia Oh recently published a study in the journal Mucosal Immunology, titled “Tuning of human MAIT cell activation by commensal bacteria species and MR1-dependent T-cell presentation.” Mucosal-associated invariant T (MAIT) cells are a type of T cell present in various sites of the body, including the gut mucosa, and defend against microbial infection by recognizing a particular bacterial metabolite shown to them by antigen presenting cells (APCs). In the gut microbiota, there are many different species of bacteria present and yet, MAIT cells don’t mount an immune response to all of them. It is therefore likely that these cells can distinguish which types of bacteria are beneficial to us and which are harmful. The findings from this study could be highly relevant for ME/CFS patients, who are thought to have disruptions of both their immune system and their microbiome.
To investigate how MAIT cells can discriminate between different species of bacteria, Derya and Julia conducted an experiment where they screened 47 different bacterial species to see how well they stimulated T cells that expressed the MAIT T-cell receptor (TCR), which is the receptor that allows MAIT cells to recognize and bind the bacterial metabolite. They found that only bacterial species that encoded the riboflavin pathway were able to stimulate the T cells. Further, the team found that activation of the T cells correlated with the level of riboflavin that each bacterial species secreted, suggesting that MAIT cells can not only discriminate between different species, but can categorize the complex gut microbiota depending on riboflavin metabolite levels, ultimately fine-tuning their responses depending on which bacterial species they come in contact with.
In a JAX research highlight article about the study, Mark Wanner notes that the ratio of different bacterial species can often be thrown off in disease states. Bacteroidetes species tend to be high stimulators of MAIT cells, which Firmicutes species are low stimulators, and he notes that, “Crohn’s disease patients exhibit an increased Bacteroidetes to Firmicutes ratio, in addition to the presence of other pro-MAIT stimulatory species. That skewing of the normal microbiome state may contribute to the chronic inflammation in the gut that’s a hallmark of the disease.” This new study is likely relevant to ME/CFS, as it shows that there is at least one clear link between the microbiome composition and perturbations to the immune system.