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Mucosal-associated invariant T-Cell (MAIT) activation is altered by chlorpyrifos- and glyphosate-treated commensal
Anne Mendler1, Florian Geier1, Sven-Bastiaan Haange2
1Department of Environmental Immunology, Helmholtz Centre for Environmental Research Leipzig - UFZ, Leipzig, Germany.
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.
Insights
Pesticides chlorpyrifos (CPF) and glyphosate (GLP) alter gut bacteria metabolism, affecting mucosal-associated invariant T-cell (MAIT) activity. CPF exposure increased pro-inflammatory MAIT responses by changing riboflavin and folate production in gut bacteria.
Area of Science:
- Microbiology
- Immunology
- Toxicology
Background:
- Gut microbiota produce metabolites crucial for mucosal-associated invariant T-cells (MAIT).
- Pesticides like chlorpyrifos (CPF) and glyphosate (GLP) are known to disrupt gut microbiota composition and function.
- MAIT cells play a role in immune surveillance and response to microbial metabolites.
Purpose of the Study:
- To investigate the impact of CPF and GLP on gut microbiota metabolism.
- To determine how these pesticides affect bacteria-mediated modulation of MAIT cell activity.
- To explore the link between pesticide exposure, microbial metabolism, and immune response.
Main Methods:
- Treatment of representative gut bacteria (Bifidobacterium adolescentis, Lactobacillus reuteri, Escherichia coli) with CPF or GLP.
- MAIT cell stimulation assays using treated bacteria.
- Analysis of riboflavin and folate production by bacteria.
- Proteomic analysis of pesticide-treated bacteria.
Main Results:
- Escherichia coli activated MAIT cells, while Bifidobacterium adolescentis and Lactobacillus reuteri inhibited activation.
- CPF significantly enhanced E. coli-mediated MAIT cell activation.
- CPF and GLP weakened the inhibitory effect of B. adolescentis and L. reuteri on MAIT cells.
- CPF altered riboflavin and folate production in bacteria, impacting MAIT cell responses.
- Proteomic analysis revealed changes in riboflavin and folate biosynthesis pathways in CPF-treated E. coli.
Conclusions:
- CPF and GLP can alter the metabolism of key gut bacteria.
- These alterations can lead to dysregulated MAIT cell activity, potentially promoting pro-inflammatory immune responses.
- The findings highlight the potential immunotoxic effects of pesticide exposure via gut microbiota modulation.
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