Deoxynivalenol(DON) and related compounds target protein processing to induce immunotoxic effects in human T cells and macrophages [M2]

Deoxynivalenol (DON) is a fungal toxin mainly produced by Fusarium graminearum and Fusarium graminearum, and is present in cereal crops such as wheat, barley, oats, rye, and corn. It is widely polluted worldwide. DON and its related derivatives have a wide range of toxic effects on humans and animals. This study used zebrafish models and different cell models to verify the toxic effects of DON, and explored the mechanism of DON mediated Jurkat apoptosis and inhibition of M2 macrophage differentiation. The results indicate that the toxic effects of these fungal toxins differ significantly among various cell types. For Jurkat T cells, the IC50 values of DON, NIV, 15 Ac DON, and 3-Ac DON were 488.6 nM, 318.2 nM, 544 nM, and 6516 nM, respectively. There are significant differences in the effects on M2 polarization of macrophages, and DON, NIV, and 15 Ac DON can inhibit M2 differentiation and function of macrophages at lower dose levels. Indicating that immune toxicity is an important toxic effect of DON and its related substances. Research on its mechanism has shown that DON can target protein processing processes, interfere with the normal synthesis and folding of proteins in cells, and trigger cellular stress responses. These findings reveal the toxic effects and potential mechanisms of DON on human immune cells, providing a scientific basis for preventing and controlling DON pollution and its harm to human health. Overall design: Study the immunotoxicity of DON and its related substances using Jurkat T cells and M2 macrophages. Total RNA was extracted using TRIzol for transcriptome sequencing, and three biological replicates were set for Jurkat T cells and M2 macrophages.