Immunotoxic effect and mechanisms of Fusarium mycotoxins on human immune cells: A focus on T cells and macrophages.

Fusarium mycotoxins, including deoxynivalenol (DON), 15-acetyl-deoxynivalenol (15-Ac-DON), 3-acetyl-deoxynivalenol (3-Ac-DON), and nivalenol (NIV), are prevalent contaminants in food and animal feed, posing significant health risks to humans. Although immunotoxicity is acknowledged as a sensitive endpoint for DON exposure, the immunotoxic effects and mechanisms of its acetylated derivatives and NIV, especially in human-derived immune cells, are not fully elucidated. In this study, we explored the toxicological impacts and mechanisms of these mycotoxins on human immune cells, with a focus on T cells and macrophages. After treating human-derived cell models with four fungal toxins (0-5000 nM) for 48 h, Jurkat T cells showed heightened sensitivity to these mycotoxins, with NIV exhibiting the highest cytotoxicity, followed by DON, 15-Ac-DON, and 3-Ac-DON. Notably, these four mycotoxins dose-dependently inhibited the activation of human T cells in the Peripheral Blood Mononuclear Cells (PBMCs) model at much lower exposure levels (0-200 nM). Similarly, after treating macrophages with NIV (0-500 nM), DON (0-1000 nM), and 15-Ac-DON (0-1000 nM) for 48 h, dose-dependent inhibition of macrophage alternative activation, lysosomal biosynthesis, and cytokine production were observed. Transcriptomic analyses indicated that DON, 15-Ac-DON, and NIV disrupt ribosome biogenesis and protein processing pathways in both T cells and macrophages. These findings underscore the influence of chemical structure on the toxicity of Fusarium mycotoxins and provide critical insights into their immunotoxic mechanisms.