College of Life Sciences and Engineering, Foshan University, Foshan, 528225, Guangdong Province, PR China.
College of Life Sciences and Engineering, Foshan University, Foshan, 528225, Guangdong Province, PR China.
Dev Comp Immunol. 2022 Mar;128:104325. doi: 10.1016/j.dci.2021.104325. Epub 2021 Nov 25.
Aflatoxin B1 (AFB1) is a mycotoxin with strong toxicity and play a large proportion in aspergillosis. Heterophil extracellular traps (HETs) was considered as an innate immune response of chickens to resist pathogens. AFB1 has been reported to trigger macrophages extracellular traps (METs) in THP-1 cells and RAW264.7 cells, but whether AFB1 could also activate HETs release, and the mechanism underlying AFB1-activated HETs in chicken remains unclear. In this study, we confirmed that AFB1could induce HETs release, which was a network of DNA-based structures consist of citrullinated histone 3 (citH3) and elastase. Meanwhile, AFB1-activated HETs rely on the glycolytic process to provide energy, NADPH oxidase and p38 signaling pathway. Moreover, it has been verified that AFB1-activated HETs release could significantly increase the biochemical indexes of liver (ALT and AST) and kidney (CRE and BUN) in serum. In addition, histopathological observation showed that AFB1 caused swelling, necrosis and vacuolation of hepatocytes in liver, and necrosis, exfoliated of nephrocyte in kidney. Further investigation demonstrated that AFB1 significantly decreased the levels of SOD and GSH-PX but increased the level of MDA, and meanwhile induced the mRNA expressions of TNF-α, IL-6 and IL-1β, iNOS, COX-2, NLRP3, caspase-1, caspase-3 and caspase-11. However, all these AFB1-induced biochemical indexes and histopathological changes were effectively alleviated by DNase I (the standard degradant for HETs). In conclusion, it has preliminary confirmed that AFB1-activated HETs formation contributed to the immunotoxicity in chicken and provide new strategies for the therapy in aspergillosis.
黄曲霉毒素 B1（AFB1）是一种毒性很强的真菌毒素，在曲霉菌病中占有很大比例。嗜中性粒细胞细胞外诱捕网（HETs）被认为是鸡抵抗病原体的固有免疫反应。据报道，AFB1 可以触发 THP-1 细胞和 RAW264.7 细胞中的巨噬细胞细胞外诱捕网（METs），但 AFB1 是否也能激活 HETs 的释放，以及 AFB1 激活鸡 HETs 的机制尚不清楚。在这项研究中，我们证实 AFB1 可以诱导 HETs 的释放，这是一种由瓜氨酸化组蛋白 3（citH3）和弹性蛋白酶组成的基于 DNA 的结构网络。同时，AFB1 激活的 HETs 依赖糖酵解过程提供能量、NADPH 氧化酶和 p38 信号通路。此外，已经验证 AFB1 激活的 HETs 释放可以显著增加血清中肝脏（ALT 和 AST）和肾脏（CRE 和 BUN）的生化指标。此外，组织病理学观察表明，AFB1 导致肝脏肝细胞肿胀、坏死和空泡化，肾脏肾细胞坏死、脱落。进一步研究表明，AFB1 显著降低 SOD 和 GSH-PX 的水平，增加 MDA 的水平，同时诱导 TNF-α、IL-6 和 IL-1β、iNOS、COX-2、NLRP3、caspase-1、caspase-3 和 caspase-11 的 mRNA 表达。然而，DNase I（HETs 的标准降解物）有效缓解了所有这些 AFB1 诱导的生化指标和组织病理学变化。综上所述，初步证实 AFB1 激活的 HETs 形成导致了鸡的免疫毒性，并为曲霉菌病的治疗提供了新的策略。
