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

J Immunotoxicol. 2020 Dec;17(1):10-20. doi: 10.1080/1547691X.2019.1706672.

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, Bifidobacterium adolescentis (B. adolescentis), Lactobacillus reuteri (L. reuteri), and Escherichia coli (E. coli) 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 E. coli activated MAIT cells whereas B. adolescentis and L. reuteri inhibited MAIT cell activation. CPF treatment significantly increased E. coli-mediated MAIT cell activation. Treatment of B. adolescentis and L. reuteri 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 E. coli 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.

Keywords: MAIT cells; chlorpyrifos; glyphosate; gut microbiota; pesticides.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bifidobacterium adolescentis / drug effects
  • Bifidobacterium adolescentis / immunology
  • Bifidobacterium adolescentis / metabolism
  • Biosynthetic Pathways / drug effects
  • Biosynthetic Pathways / immunology
  • Blood Buffy Coat / cytology
  • Chlorpyrifos / toxicity
  • Escherichia coli / drug effects
  • Escherichia coli / immunology
  • Escherichia coli / metabolism
  • Folic Acid / analysis
  • Folic Acid / biosynthesis
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / immunology
  • Glycine / analogs & derivatives
  • Glycine / toxicity
  • Glyphosate
  • Healthy Volunteers
  • Herbicides / toxicity*
  • Host Microbial Interactions / drug effects
  • Host Microbial Interactions / immunology
  • Humans
  • Insecticides / toxicity*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Limosilactobacillus reuteri / drug effects
  • Limosilactobacillus reuteri / immunology
  • Limosilactobacillus reuteri / metabolism
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Mucosal-Associated Invariant T Cells / immunology*
  • Proteomics
  • Riboflavin / analysis
  • Riboflavin / biosynthesis

Substances

  • Herbicides
  • Insecticides
  • Folic Acid
  • Chlorpyrifos
  • Glycine
  • Riboflavin