Inflammation plays a critical role in damage to the bronchiolar epithelium induced by Trueperella pyogenes in vitro and in vivo

文献类型： 外文期刊

第一作者： Qin, Lei

作者： Qin, Lei;Meng, Fandan;Li, Siqi;Zhang, Hongliang;Sun, Yuan;An, Tongqing;Cai, Xuehui;Wang, Shujie;Qin, Lei;He, Haijuan;Zhang, Wenlong;Cai, Xuehui;Wang, Shujie

作者机构：

关键词： Trueperella pyogenes; PBECs; PCLS; infection; inflammation; intracellular pathways

期刊名称：INFECTION AND IMMUNITY （ 影响因子：3.1； 五年影响因子：3.2 ）

ISSN： 0019-9567

年卷期： 2023 年

页码：

收录情况： SCI

摘要： Trueperella pyogenes can cause severe pulmonary disease in swine, but the mechanism of pathogenesis is not well defined. T. pyogenes-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 T. pyogenes 20121 to infect PBECs in air-liquid interface conditions and porcine PCLS. T. pyogenes 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 T. pyogenes-infected mice. In addition, we used T. pyogenes 20121 to infect tumor necrosis factor-alpha (tnf-alpha-/-) mice, and the results indicated that apoptosis and injury in respiratory epithelium of infected tnf-alpha-/- mice were alleviated. Thus, the pro-inflammatory cytokine TNF-alpha played a role in apoptosis and the respiratory epithelium injury in mouse lungs. Collectively, our study provides insight into the inflammatory injury induced by T. pyogenes and suggests that blocking NLR may be a potential therapeutic strategy against T. pyogenes infection.

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