Mucosal-associated invariant T-Cell (MAIT) activation is altered by chlorpyrifos- and glyphosate-treated commensal gut bacteria

Abstract

Mucosal-associated invariant T-cells (MAIT) can react to metabolites of the vitamins riboflavin and folate which are produced by the human gut microbiota. Since several studies showed that the pesticide chlorpyrifos (CPF) and glyphosate (GLP) can impair the gut microbiota, the present study was undertaken to investigate the impact of CPF and GLP treatment on the metabolism of gut microbiota and the resulting bacteria-mediated modulation of MAIT cell activity. Here, <i>Bifidobacterium adolescentis</i> (<i>B. adolescentis</i>), <i>Lactobacillus reuteri</i> (<i>L. reuteri</i>), and <i>Escherichia coli</i> (<i>E. coli</i>) were treated with CPF (50-200 µM) or GLP (75-300 mg/L) and then used in MAIT cell stimulation assays as well as in vitamin and proteome analyses. All three bacteria were nonpathogenic and chosen as representatives of a healthy human gut microflora. The results showed that <i>E. coli</i> activated MAIT cells whereas <i>B. adolescentis</i> and <i>L. reuteri</i> inhibited MAIT cell activation. CPF treatment significantly increased <i>E. coli</i>-mediated MAIT cell activation. Treatment of <i>B. adolescentis</i> and <i>L. reuteri</i> with CPF and GLP weakened the inhibition of MAIT cell activation. Riboflavin and folate production by the test bacteria was influenced by CPF treatment, whereas GLP had only minor effects. Proteomic analysis of CPF-treated <i>E. coli</i> revealed changes in the riboflavin and folate biosynthesis pathways. The findings here suggest that the metabolism of the analyzed bacteria could be altered by exposure to CPF and GLP, leading to an increased pro-inflammatory immune response.