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

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.脱氧雪腐镰刀菌烯醇（Deoxynivalenol, DON）是一类主要由禾谷镰孢菌（Fusarium graminearum）产生的真菌毒素，广泛存在于小麦、大麦、燕麦、黑麦、玉米等谷类作物中，其污染范围遍布全球。DON及其相关衍生物对人类与动物具有广泛的毒性作用。本研究采用斑马鱼模型与多种细胞模型，验证了DON的毒性效应，并探究了DON介导Jurkat细胞凋亡及抑制M2型巨噬细胞分化的分子机制。研究结果显示，这类真菌毒素的毒性效应在不同细胞类型间存在显著差异：针对Jurkat T细胞，DON、雪腐镰刀菌烯醇（Nivalenol, NIV）、15-乙酰基脱氧雪腐镰刀菌烯醇（15-Ac DON）及3-乙酰基脱氧雪腐镰刀菌烯醇（3-Ac DON）的半最大效应浓度（IC50）分别为488.6 nM、318.2 nM、544 nM及6516 nM。这类毒素对巨噬细胞M2极化的影响亦存在显著差异，其中DON、NIV及15-Ac DON可在较低剂量水平下抑制巨噬细胞的M2型分化与功能。这表明免疫毒性是DON及其相关衍生物的重要毒性效应之一。相关机制研究显示，DON可靶向作用于细胞内蛋白质加工过程，干扰细胞内蛋白质的正常合成与折叠，并诱发细胞应激反应。本研究结果阐明了DON对人类免疫细胞的毒性效应及其潜在作用机制，为防控DON污染及其对人类健康造成的危害提供了科学依据。研究整体设计：以Jurkat T细胞与M2型巨噬细胞为模型，探究DON及其相关衍生物的免疫毒性；采用TRIzol法提取总RNA进行转录组测序，Jurkat T细胞与M2巨噬细胞样本均设置3次生物学重复。