Mucosa-associated invariant T (MAIT) cells are antimicrobial, innate-like T cells that recognize riboflavin-related metabolites produced by diverse bacteria. MAIT cells are highly abundant in human peripheral blood and mucosal tissues. These cells mediate antimicrobial activity through the production of pro-inflammatory cytokines, cytotoxic proteins, and direct bacterial killing. Lacticaseibacillus rhamnosus GG (LGG) is a probiotic strain with a potent immune regulation function. However, there is a paucity of knowledge on how LGG mediates its immunomodulatory activity. Here, we investigated the interaction between MAIT cells with LGG and the intestinal pathobiont Escherichia coli.
Initially, we established a co-culture system to investigate the direct interactions between LGG and MAIT cells. The antimicrobial responses of MAIT cells in co-culture with LGG alone were attenuated, showing a weak activation phenotype with low expression of IFNγ and TNF. In the presence of IL-2 and IL-7, LGG significantly enhances the cytotoxic capabilities of MAIT cells by markedly increasing the expression of Granzyme B, IFNγ, and TNF. Next, we investigated the effect of LGG on MAIT cell effector activity following E. coli stimulations. MAIT cells produced pro-inflammatory cytokines and cytolytic proteins following E. coli stimulations in a dose-dependent manner. However, in the presence of LGG, MAIT cell activation was downregulated with a decrease in CD69, IFNγ, and TNF levels. Additionally, apparent decrease in degranulation and Granzyme B expression indicate a potential reduction in MAIT cell ability to kill E. coli-infected cells effectively.
These results indicate that LGG has the capacity to dampen MAIT cells-mediated inflammatory and cytotoxic responses against E. coli. Understanding Lacticaseibacillus-mediated modulation of MAIT cell function may pave a better treatment pathway in disease settings where overexuberant immune responses against commensal or pathobiont bacteria plays a major contributing factor, such as in inflammatory bowel disease (IBD).