State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China.
Laboratory Animal Centre, Qiqihar Medical University, Qiqihar, China.
Infect Immun. 2023 Dec 12;91(12):e0027323. doi: 10.1128/iai.00273-23. Epub 2023 Nov 6.
can cause severe pulmonary disease in swine, but the mechanism of pathogenesis is not well defined. induced damage to porcine bronchial epithelial cells (PBECs), porcine precision-cut lung slices (PCLS), and respiratory epithelium of mice remains unknown. In this study, we used 20121 to infect PBECs in air-liquid interface conditions and porcine PCLS. could adhere to, colonize, and induce cytotoxic effect on PBECs and the luminal surface of bronchi in PCLS, which damaged the bronchiolar epithelium. Moreover, bronchiolar epithelial cells showed extensive degeneration in the lungs of infected mice. Furthermore, western blot showed that the NOD-like receptor (NLR)/C-terminal caspase recruitment domain (ASC)/caspase-1 axis and nuclear factor-kappa B pathway were involved in inflammation in PCLS and lungs of mice, which also confirms that porcine PCLS provide a platform to analyze the pulmonary immune response. Meanwhile, the levels of p-c-Jun N-terminal kinase, p-extracellular signal-regulated kinase, and p-protein kinase B (AKT) were increased significantly, which indicated the mitogen-activated protein kinase and Akt pathways were also involved in inflammation in infected mice. In addition, we used 20121 to infect tumor necrosis factor-alpha (tnf-α) mice, and the results indicated that apoptosis and injury in respiratory epithelium of infected tnf-α mice were alleviated. Thus, the pro-inflammatory cytokine TNF-α played a role in apoptosis and the respiratory epithelium injury in mouse lungs. Collectively, our study provides insight into the inflammatory injury induced by and suggests that blocking NLR may be a potential therapeutic strategy against infection.
可引起猪的严重肺部疾病，但发病机制尚不清楚。 对猪支气管上皮细胞（PBEC）、猪精密切割肺切片（PCLS）和小鼠呼吸道上皮的诱导损伤尚不清楚。在这项研究中，我们使用 20121 感染气液界面条件下的 PBEC 和猪 PCLS。 可以黏附、定植并诱导 PBEC 和 PCLS 中支气管的腔面产生细胞毒性作用，从而损害细支气管上皮。此外，感染小鼠的肺部中细支气管上皮细胞广泛退化。此外，Western blot 显示，NOD 样受体（NLR）/C 末端衔接蛋白（ASC）/半胱天冬酶-1 轴和核因子-κB 途径参与了 PCLS 和小鼠肺部的炎症反应，这也证实了猪 PCLS 提供了一个平台来分析肺部免疫反应。同时，p-c-Jun N 末端激酶、p-细胞外信号调节激酶和 p-蛋白激酶 B（AKT）的水平显著增加，表明丝裂原活化蛋白激酶和 Akt 途径也参与了感染小鼠的炎症反应。此外，我们使用 20121 感染肿瘤坏死因子-α（tnf-α）小鼠，结果表明感染 tnf-α 小鼠的呼吸上皮细胞凋亡和损伤减轻。因此，促炎细胞因子 TNF-α在感染小鼠肺部的细胞凋亡和呼吸上皮损伤中发挥作用。总之，我们的研究提供了对 引起的炎症性损伤的深入了解，并表明阻断 NLR 可能是对抗 感染的潜在治疗策略。
