低剂量脱氧雪腐镰刀菌烯醇通过激活巨自噬/NLRP3炎症小体加重产肠毒素大肠杆菌感染引起的肠道炎症和屏障功能障碍,Journal of Agricultural and Food Chemistry

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低剂量脱氧雪腐镰刀菌烯醇通过激活巨自噬/NLRP3炎症小体加重产肠毒素大肠杆菌感染引起的肠道炎症和屏障功能障碍
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-02-24 , DOI: 10.1021/acs.jafc.1c07834
Lei Ge _{1,

2,

3} , Dandan Liu _{1,

2,

3} , Xinru Mao _{1,

2,

3} , Shuiping Liu _{1,

2,

3} , Junyan Guo _{1,

2,

3} , Lili Hou _{1,

2,

3} , Xingxiang Chen _{1,

2,

3} , Kehe Huang _{1,

2,

3}

Affiliation

脱氧雪腐镰刀菌烯醇 (DON) 对健康人和动物的毒性已被广泛研究。然而，在不健康的条件下，尤其是肠道损伤，天然低剂量的 DON 是否毫发无损，尚不清楚。产肠毒素大肠埃希菌感染(ETEC) 是一种经典的肠道损伤模型。在这项研究中，我们探讨了低剂量 DON 对 ETEC 感染引起的肠道损伤的影响以及仔猪、小鼠和 IPEC-J2 单层细胞的潜在机制。结果表明，实验组（低剂量DON，仔猪饲料中0.75 mg/kg，小鼠1 mg/kg体重，与 ETEC 感染相结合）。同时，在动物和 IPEC-J2 单层细胞中观察到更严重的肠道炎症和屏障功能障碍。实验组在空肠和IPEC-J2中观察到NLRP3炎性体和LC3B的表达水平较高。用 NLRP3 或 caspase1 抑制剂治疗后，实验组肠道炎症过度而不是屏障功能障碍受到限制。CRISPR-Cas9 介导的 LC3B 敲除减轻了肠道炎症和屏障功能障碍，还抑制了 NLRP3 炎性体。总之，低剂量的 DON 通过激活巨自噬和 NLRP3 炎性体来加重由 ETEC 感染引起的肠道炎症和屏障功能障碍。

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Low Dose of Deoxynivalenol Aggravates Intestinal Inflammation and Barrier Dysfunction Induced by Enterotoxigenic Escherichia coli Infection through Activating Macroautophagy/NLRP3 Inflammasomes

The toxicity of deoxynivalenol (DON) in healthy humans and animals has been extensively studied. However, whether the natural-low-dose DON is scatheless under unhealthy conditions, especially intestinal injury, is unknown. Infection of enterotoxigenic Escherichia coli (ETEC) is a classical intestinal injury model. In this study, we explored the effects of low-dose DON on intestinal injury induced by the ETEC infection and the underlying mechanism in piglets, mice, and IPEC-J2 monolayer cells. Results showed that significant growth slowdown, severe diarrhea, and intestinal damage, bacterial multiplication, and translocation were observed in the experimental group (low-dose DON, 0.75 mg/kg in feed for piglets, and 1 mg/kg body weight for mice, combined with the ETEC infection). Meanwhile, more aggressive intestinal inflammation and barrier dysfunction were observed in animals and IPEC-J2 monolayer cells. Higher expression levels of NLRP3 inflammasome and LC3B were observed in jejunum and IPEC-J2 in the experimental group. After treatment with NLRP3 or caspase1 inhibitors, excessive intestinal inflammation rather than barrier dysfunction in the experimental group was limited. CRISPR-Cas9-mediated knockout of LC3B alleviated intestinal inflammation and barrier dysfunction and also inhibited NLRP3 inflammasome. In conclusion, a low dose of DON aggravates intestinal inflammation and barrier dysfunction induced by the ETEC infection by activating macroautophagy and NLRP3 inflammasome.

更新日期：2022-02-24

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