Institute of Food Safety and Health, College of Public Health, National Taiwan University, Taipei 10055, Taiwan.
Institute of Food Safety and Health, College of Public Health, National Taiwan University, Taipei 10055, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei 10055, Taiwan.
Ecotoxicol Environ Saf. 2024 Mar 1;272:116085. doi: 10.1016/j.ecoenv.2024.116085. Epub 2024 Feb 10.
Zearalenone (ZEN) is a prevalent mycotoxin that severely impacts human and animal health. However, the possible interactions between ZEN exposure, pathogen infection, immune system, and reactive oxygen species (ROS) were rarely investigated. We studied the effects of early-life ZEN (50 µM) exposure on the immune response of Caenorhabditis elegans against Bacillus thuringiensis infection and the associated mechanisms. The transcriptomic responses of C. elegans after early-life ZEN exposure were investigated using RNA sequencing and followed by verification using quantitative PCR analysis. We also investigated the immune responses of the worms through B. thuringiensis killing assays and by measuring oxidative stress. The transcriptomics result showed that early-life exposure to ZEN resulted in 44 differentially expressed genes, 7 of which were protein-coding genes with unknown functions. The Gene Ontology analysis suggested that metabolic processes and immune response were among the most significantly enriched biological processes, and the KEGG analysis suggested that lysosomes and metabolic pathways were the most significantly enriched pathways. The ZEN-exposed worms exhibited significantly reduced survival after 24-h B. thuringiensis infection, reaching near 100% mortality compared to 60% of the controls. Using qRT-PCR assay, we found that ZEN further enhanced the expression of immunity genes lys-6, spp-1, and clec-60 after B. thuringiensis infection. A concurrently enhanced ROS accumulation was also observed for ZEN-exposed worms after B. thuringiensis infection, which was 1.2-fold compared with the controls. Moreover, ZEN exposure further enhanced mRNA expression of catalases (ctl-1 and ctl-2) and increased catalase protein activity after B. thuringiensis exposure compared with their non-exposed counterparts, suggesting an elevated oxidative stress. This study suggests that early-life exposure to mycotoxin zearalenone overstimulates immune responses involving spp-17, clec-52, and clec-56, resulting in excessive ROS production, enhanced oxidative stress as indicated by aggravated ctl expression and activity, and a decline in host resistance to pathogenic infection which ultimately leads to increased mortality under B. thuringiensis infection. Our findings provide evidence that could improve our understanding on the potential interactions between mycotoxin zearalenone and pathogens.
玉米赤霉烯酮（ZEN）是一种普遍存在的真菌毒素，严重影响人类和动物的健康。然而，ZEN 暴露、病原体感染、免疫系统和活性氧（ROS）之间的可能相互作用很少被研究。我们研究了早期生活中 ZEN（50µM）暴露对秀丽隐杆线虫对抗苏云金芽孢杆菌感染的免疫反应的影响，以及相关的机制。使用 RNA 测序研究了早期生活中 ZEN 暴露后秀丽隐杆线虫的转录组反应，并通过定量 PCR 分析进行了验证。我们还通过苏云金芽孢杆菌杀伤试验和测量氧化应激来研究线虫的免疫反应。转录组学结果表明，早期生活中 ZEN 的暴露导致 44 个差异表达基因，其中 7 个是具有未知功能的蛋白质编码基因。GO 分析表明，代谢过程和免疫反应是最显著富集的生物学过程之一，KEGG 分析表明，溶酶体和代谢途径是最显著富集的途径。与对照组的 60%相比，暴露于 ZEN 的线虫在 24 小时苏云金芽孢杆菌感染后存活率显著降低，接近 100%的死亡率。使用 qRT-PCR 测定，我们发现 ZEN 在苏云金芽孢杆菌感染后进一步增强了免疫基因 lys-6、spp-1 和 clec-60 的表达。在苏云金芽孢杆菌感染后，还观察到 ZEN 暴露的线虫 ROS 积累增加，与对照组相比增加了 1.2 倍。此外，与未暴露的对照组相比，ZEN 暴露后苏云金芽孢杆菌暴露进一步增加了过氧化氢酶（ctl-1 和 ctl-2）的 mRNA 表达，并增加了过氧化氢酶蛋白的活性，表明氧化应激增加。这项研究表明，早期生活中接触真菌毒素玉米赤霉烯酮会过度刺激涉及 spp-17、clec-52 和 clec-56 的免疫反应，导致过多的 ROS 产生，增强氧化应激，如 ctl 表达和活性的加重所示，并降低宿主对致病性感染的抵抗力，最终导致苏云金芽孢杆菌感染下死亡率增加。我们的研究结果提供了证据，可以提高我们对真菌毒素玉米赤霉烯酮和病原体之间潜在相互作用的理解。
