Dietary exposure to chlorpyrifos affects systemic and hepatic immune-cell phenotypes in diabetic mice

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Abstract

Hyperglycemia induces low-grade systemic inflammation and immune dysregulation, leading to overstated reactions to immune stimuli and diabetes-related organ damage. Tissue inflammation is characterized by leukocyte infiltration, and T cells play crucial roles in directing leukocyte-mediated inflammatory responses. The aim of the study was to investigate the effects of dietary exposure to chlorpyrifos (CPF) on systemic and hepatic immune-cell phenotypes in C57BL/6 mice with streptozotocin (STZ)-induced diabetes. Mice received an intraperitoneal injection of STZ for 5 consecutive days to induce diabetes, and diabetic mice were given either an AIN-93-based control diet or a CPF-containing diet at doses of 0.5, 1, or 2 mg/kg body weight/day for 28 days. Results showed that dietary exposure to CPF had no influence on the body weight or the erythrocyte hemoglobin A1c level in diabetic mice. Both blood and hepatic neutrophil populations were enhanced by CPF exposure. CPF-exposed groups had lower percentages of blood T cells without altering the proportions of CD4+ and CD8+ T-cell subsets, and lower expression levels of the Bcl-2 antiapoptotic gene in the spleen. CPF exposure reduced the percentage of blood regulatory T cells (Tregs); however, the Treg population was upregulated in the liver even when hepatic T cells were not affected by CPF in diabetic mice. Hepatic expressions of Treg-related genes were suppressed in all CPF-exposed groups. Higher plasma levels of aspartate aminotransferase and expression levels of the hepatic interleukin-1β gene were observed in diabetic mice exposed to medium and high doses of CPF. These findings suggest that dietary exposure to CPF affects the distribution of both myeloid and lymphoid immune cells in the blood and liver under hyperglycemic conditions, which may lead to hyperinflammation when encountering immune stimuli.

Original languageEnglish
Article number152698
JournalToxicology
Volume452
DOIs
Publication statusPublished - Mar 30 2021

Keywords

  • Chlorpyrifos
  • Hyperglycemia
  • Immune cells
  • Inflammation
  • Liver
  • Regulatory T cells

ASJC Scopus subject areas

  • Toxicology

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