Glycolysis and Reactive Oxygen Species Production Participate in T-2 Toxin-Stimulated Chicken Heterophil Extracellular Traps.
Glycolysis and Reactive Oxygen Species Production Participate in T-2 Toxin-Stimulated Chicken Heterophil Extracellular Traps.
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DOI：
10.1021/acs.jafc.1c05371
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发表时间：
2021-10
影响因子：
6.1
通讯作者：
Wei Liu;Di Wu;Shuangqiu Li;Jingnan Xu;Peixuan Li;Aimin Jiang;Yong Zhang;Ziyi Liu;Liqiang J
中科院分区：
文献类型：
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作者：
Wei Liu;Di Wu;Shuangqiu Li;Jingnan Xu;Peixuan Li;Aimin Jiang;Yong Zhang;Ziyi Liu;Liqiang J
T-2毒素(T-2)是由镰刀菌产生的一种毛霉烯类毒素，是一种危害家禽和人类健康的环境污染物。异嗜性细胞外陷阱不仅是鸡抵御病原体感染的一种免疫防御方式，而且还参与了多种疾病的病理生理机制。然而，T-2在体外对HET形成的免疫毒性尚未见报道。在本研究中，异嗜性细胞暴露于T-2，剂量分别为20，40和80 ng/mL，作用90分钟。免疫荧光染色观察HETs的结构，并用抑制剂和PicoGreen分析HETs的形成机制。这些结果表明，T-2触发的HET的形成由DNA、弹性蛋白酶和CitH3组成。此外，T-2诱导的HETs的产生也被糖酵解、烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶、p38和细胞外信号调节激酶(ERK)1/2信号通路的抑制剂所抑制，提示T-2诱导的HETs与糖酵解、ROS的产生、ERK1/2和p38信号通路以及NADPH氧化酶有关。综上所述，本研究阐明了T-2触发HET形成的机制，并可能为理解T-2对鸡早期先天免疫的免疫毒性提供新的视角。
T-2 toxin (T-2) is a kind of trichothecene toxin produced from Fusarium fungi, which is an environmental pollutant that endangers poultry and human health. Heterophil extracellular traps (HETs) are not only a form of chicken immune defense against pathogen infection but also involved in pathophysiological mechanisms of several diseases. However, the immunotoxicity of T-2 on HET formation in vitro has not yet been reported. In this study, heterophils were exposed to T-2 at doses of 20, 40, and 80 ng/mL for 90 min. Observation of the structure of HETs by immunofluorescence staining and the mechanism of HET formation was analyzed by inhibitors and PicoGreen. These results showed that T-2-triggered HET formation consisted of DNA, elastase, and citH3. Furthermore, T-2 increased reactive oxygen species (ROS) generation, and the formation of T-2-triggered HETs was also decreased by the inhibitors of glycolysis, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p38 and extracellular signal-regulated kinase (ERK)1/2 signaling pathways, suggesting that T-2-induced HETs are associated with glycolysis, ROS production, ERK1/2 and p38 signaling pathways, and NADPH oxidase. Taken together, this study elucidates the mechanism of T-2-triggered HET formation, and it may provide new insight into understanding the immunotoxicity of T-2 to early innate immunity in chickens.