School of Life Sciences and Engineering , Foshan University , Foshan 528225 , Guangdong Province , China.
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine , Jilin University , Changchun 130062 , Jilin Province , PR China.
J Agric Food Chem. 2019 Oct 9;67(40):11230-11235. doi: 10.1021/acs.jafc.9b03155. Epub 2019 Sep 27.
Ochratoxin A (OTA) is a mycotoxin which could cause strong immunosuppressive toxicological effects in animals and humans. Heterophil extracellular traps (HETs) as a novel defense of chicken heterophils play an important role against pathogen infection. It has been reported that OTA can weaken the phagocytosis function of neutrophils. However, whether or not OTA shows immunosuppressive effects on HET release remains unclear. In the present study, we aim to first investigate the effects of OTA on HET release and then try to clarify the mechanisms in this process. OTA-induced HET structures were observed and analyzed by fluorescence confocal microscopy. The quantitative determination of OTA-induced HETs was measured by PicoGreen and a fluorescence microplate. The results clearly showed that OTA obviously induced the release of HET-like structures in heterophils, and these extracellular networks were composed by chromatin decorated with histones and neutrophil elastase. Reactive oxygen species (ROS) production was also increased in the process of OTA-induced HET formation. Furthermore, the inhibitors of NADPH oxidase, ERK [Formula: see text], and p38 MAPK signaling pathways significantly decreased OTA-induced HET formation. The abovementioned results suggest that OTA-induced HET formation is related to ROS production dependent on the activation of NADPH oxidase, ERK [Formula: see text], and p38 MAPK signaling pathways. Taken together, this study first shows that OTA possesses the ability to trigger HET formation, which provides our understanding of the host that continuously suffered OTA exposure leading to the hyporeactivity of the immune system against infection.
赭曲霉毒素 A（OTA）是一种真菌毒素，可对动物和人类产生强烈的免疫抑制毒性作用。嗜中性粒细胞细胞外诱捕网（HET）作为鸡嗜中性粒细胞的一种新型防御机制，在抵御病原体感染方面发挥着重要作用。据报道，OTA 可削弱中性粒细胞的吞噬功能。然而，OTA 是否对 HET 释放表现出免疫抑制作用尚不清楚。在本研究中，我们旨在首先研究 OTA 对 HET 释放的影响，然后尝试阐明该过程中的机制。通过荧光共聚焦显微镜观察和分析 OTA 诱导的 HET 结构。通过 PicoGreen 和荧光微孔板定量测定 OTA 诱导的 HET。结果清楚地表明，OTA 明显诱导嗜中性粒细胞释放 HET 样结构，这些细胞外网络由染色质和中性粒细胞弹性蛋白酶组成。在 OTA 诱导 HET 形成过程中还增加了活性氧（ROS）的产生。此外，NADPH 氧化酶、ERK [Formula: see text] 和 p38 MAPK 信号通路抑制剂显著降低了 OTA 诱导的 HET 形成。上述结果表明，OTA 诱导的 HET 形成与 ROS 产生有关，这依赖于 NADPH 氧化酶、ERK [Formula: see text] 和 p38 MAPK 信号通路的激活。总之，本研究首次表明 OTA 具有触发 HET 形成的能力，这有助于我们了解宿主在持续暴露于 OTA 后免疫系统对感染的反应性降低的情况。
