Transmissible gastroenteritis virus (TGEV) is a coronavirus, which causes fatal severe diarrhea and leads to high mortality in newborn piglets. Inflammasomes are hub molecules that induce proinflammatory cytokine production and maturation to initiate innate immune defenses upon cellular infection. To date, the potential role of inflammasome in TGEV infection in porcine intestinal epithelial cells has not been elucidated. The present study aims to investigate the function of the inflammasome in response to TGEV infection in porcine intestinal epithelial cells. Our results revealed that TGEV infection induced the production of pro-interleukin-1β (pro-IL-1β) and enhanced its processing and maturation in porcine intestinal epithelial cells through caspase-1 activation. In addition, TGEV infection in porcine intestinal epithelial cells induced pyroptosis, indicated by cell death and the production and cleavage of gasdermin D (GSDMD). Meanwhile, TGEV infection sufficiently activated the expression and assembly of the NOD-like receptor protein 3 (NLRP3) inflammasome in porcine intestinal epithelial cells, and inhibition of NLRP3 blocked TGEV-induced IL-1β release. We also found that inhibition of NLRP3 enhanced the replication of TGEV without inducing cell death. In conclusion, these data demonstrated that activation of IL-1β release and pyroptosis is dependent on NLRP3 inflammasome, thus NLRP3 inflammasome may play a central role in the innate immune response to TGEV infection.

中文翻译：

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传染性胃肠炎病毒对白细胞介素 1β 释放和细胞焦亡的激活依赖于猪肠上皮细胞系中的 NOD 样受体蛋白 3 炎性体

传染性胃肠炎病毒 (TGEV) 是一种冠状病毒，可导致致命的严重腹泻并导致新生仔猪的高死亡率。炎性体是中枢分子，可诱导促炎细胞因子的产生和成熟，以在细胞感染时启动先天免疫防御。迄今为止，炎症小体在猪肠上皮细胞中 TGEV 感染中的潜在作用尚未阐明。本研究旨在研究炎症小体对猪肠上皮细胞中 TGEV 感染的反应。我们的结果表明，TGEV 感染诱导了白细胞介素原 1 β（pro-IL-1 β) 并通过 caspase-1 激活增强其在猪肠上皮细胞中的加工和成熟。此外，猪肠上皮细胞中的 TGEV 感染会诱导细胞焦亡，这表现为细胞死亡和 Gasdermin D (GSDMD) 的产生和裂解。同时，TGEV感染充分激活了猪肠上皮细胞中NOD样受体蛋白3（NLRP3）炎症小体的表达和组装，抑制NLRP3可阻断TGEV诱导的IL- 1β释放。我们还发现 NLRP3 的抑制增强了 TGEV 的复制而不诱导细胞死亡。总之，这些数据表明 IL-1 β 的激活 NLRP3 炎症小体的释放和细胞焦亡依赖于 NLRP3 炎症小体，因此 NLRP3 炎症小体可能在对 TGEV 感染的先天免疫反应中起核心作用。