Yang Jing, Wang Xiaohong, Zhang Qiannan, Cui Hongyang, You Lijuan, Zhuang Zhisen, Tian Yaru, Han Xiaomin, Shi Miaoying, Bai Li, Jia Xudong, Yang Hui
School of Public Health, Shandong Second Medical University, Shandong 261053, China.
NHC Key Lab of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, Beijing 100021, China.
Toxicology. 2025 Aug;515:154170. doi: 10.1016/j.tox.2025.154170. Epub 2025 May 2.
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.
镰刀菌霉菌毒素，包括脱氧雪腐镰刀菌烯醇（DON）、15-乙酰基-脱氧雪腐镰刀菌烯醇（15-Ac-DON）、3-乙酰基-脱氧雪腐镰刀菌烯醇（3-Ac-DON）和雪腐镰刀菌烯醇（NIV），是食品和动物饲料中普遍存在的污染物，对人类健康构成重大风险。尽管免疫毒性被认为是DON暴露的一个敏感终点，但其乙酰化衍生物和NIV的免疫毒性作用及机制，尤其是在人源免疫细胞中的情况，尚未完全阐明。在本研究中，我们探讨了这些霉菌毒素对人免疫细胞的毒理学影响及机制，重点关注T细胞和巨噬细胞。在用四种真菌毒素（0 - 5000 nM）处理人源细胞模型48小时后，Jurkat T细胞对这些霉菌毒素表现出更高的敏感性，其中NIV的细胞毒性最高，其次是DON、15-Ac-DON和3-Ac-DON。值得注意的是，这四种霉菌毒素在低得多的暴露水平（0 - 200 nM）下，就能剂量依赖性地抑制外周血单核细胞（PBMCs）模型中人类T细胞的活化。同样，在用NIV（0 - 500 nM）、DON（0 - 1000 nM）和15-Ac-DON（0 - 1000 nM）处理巨噬细胞48小时后，观察到剂量依赖性地抑制巨噬细胞的替代活化、溶酶体生物合成和细胞因子产生。转录组分析表明，DON、15-Ac-DON和NIV破坏了T细胞和巨噬细胞中的核糖体生物合成和蛋白质加工途径。这些发现强调了化学结构对镰刀菌霉菌毒素毒性的影响，并为其免疫毒性机制提供了关键见解。
