Two-way immune effects of deoxynivalenol in weaned piglets and porcine alveolar macrophages: Due mainly to its exposure dosage
Two-way immune effects of deoxynivalenol in weaned piglets and porcine alveolar macrophages: Due mainly to its exposure dosage
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脱氧雪腐镰刀菌烯醇对断奶仔猪和猪肺泡巨噬细胞的双向免疫作用：主要归因于其暴露剂量
DOI：
10.1016/j.chemosphere.2020.126464
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发表时间：
2020-06-01
期刊：
影响因子：
8.8
通讯作者：
Huang, Kehe
中科院分区：
文献类型：
--
作者：
Liu, Dandan;Wang, Qing;Huang, Kehe
真菌毒素是由真菌产生的有毒代谢物，经常出现在世界各地的谷物和动物饲料中，对人类和动物构成严重威胁。虽然一些研究显示了真菌毒素的免疫毒性，但很少有研究关注真菌毒素对体外和体内免疫反应的双向影响。本研究探讨了分布最广泛的真菌毒素之一脱氧雪腐菌醇（DON）对仔猪和猪肺泡巨噬细胞（pam）免疫功能的影响，发现其在不同暴露剂量下表现出双向免疫效应。结果显示，低剂量DON增加了仔猪和PAMs中tnf - α和IL-6的表达，促进了PAMs的趋化和吞噬作用，使巨噬细胞转化为M1表型（P < 0.05）。相反，高剂量DON增加了仔猪和PAMs中tgf - β和IL-10的表达，抑制了PAMs的趋化和吞噬作用，诱导巨噬细胞m2型极化（P < 0.05）。在机制上，DON暴露在低剂量下显著激活TLR4/NF κ B通路，高剂量下诱导线粒体自噬介导的线粒体功能障碍。利用TLR4干扰和线粒体自噬激活剂CCCP进一步证实了它们的作用。因此，我们得出结论，低剂量DON暴露通过激活TLR4/NF κ B引起免疫刺激，而高剂量DON暴露通过阻断线粒体自噬引起免疫抑制。我们的研究表明，高剂量和低剂量的真菌毒素污染都可能是有害的，并进一步支持采取警惕态度以尽量减少人类和动物在环境中摄入真菌毒素的必要性。(C) 2020 Elsevier Ltd.版权所有。
Mycotoxins are toxic metabolites produced by fungal species that occur frequently in cereals and animal forages throughout the world, posing a serious threat to humans and animals. Although some studies showed the immunotoxicity of mycotoxins, little research focused on the two-way effects of mycotoxins on immune response in vitro and vivo. Here, we explored the effects of deoxynivalenol (DON), one of the most widely distributed mycotoxins, on immune function of piglets and porcine alveolar macrophages (PAMs), and found it exhibited bidirectional immune effects due to different exposure doses. Our results revealed that low doses of DON increased the expressions of TNF-alpha and IL-6 in piglets and PAMs, promoted the chemotaxis and phagocytosis of PAMs and transformed macrophages to M1 phenotype (P < 0.05). Conversely, high doses of DON increased the expressions of TGF-beta and IL-10 in piglets and PAMs, inhibited the chemotaxis and phagocytosis of PAMs and induced macrophages M2-type polarization (P < 0.05). Mechanistically, DON exposure significantly activated the TLR4/NF kappa B pathway at low doses and induced mitophagy-mediated mitochondrial dysfunction at high doses in vitro and vivo. TLR4 interference and mitophagy activator, CCCP, were used to further confirm their roles. Therefore, we concluded that DON exposure at low doses caused immunostimulation via activating TLR4/NF kappa B, whereas it was immunoinhibitory at high doses through blocking mitophagy. Our study suggested that both high and low doses mycotoxins contamination might be harmful, and further back up the necessity to take a vigilant attitude to minimize humans and animals intake of mycotoxins in the environment. (C) 2020 Elsevier Ltd. All rights reserved.