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bioRxiv · 10.1101/2023.07.24.550341

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

Qin, L.·Meng, F.·He, H.·Li, S.·Zhang, H.·Sun, Y.·Zhang, W.·An, T.-Q.·Cai, X.·Wang, S.
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Abstract

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 infected mice lungs. Furthermore, western blot showed the NOD-like receptor (NLR)/ C-terminal caspase recruitment domain (ASC)/caspase-1 axis and nuclear factor-kappa B (NF-{kappa}B) pathway were involved in inflammation in PCLS and lungs of mice, which also confirms PCLS provide a platform to analyze pulmonary immune response. Meanwhile, the levels of p-c-Jun N-terminal kinase (JNK), p-extracellular signal-regulated kinase (ERK) and p-protein kinase B (AKT) were increased significantly, which indicated the mitogen-activated protein kinase (MAPK) and Akt pathways were also involved of inflammation in T. pyogenes-infected mice. In addition, we used T. pyogenes 20121 to infect tumour necrosis factor alpha (TNF-)-/- mice, the results indicated apoptosis and injury in respiratory epithelium of infected TNF--/- mice were alleviated. Thus, pro-inflammatory cytokine TNF- played a role in apoptosis and respiratory epithelium injury of mice lungs. Collectively, our study provides an insight into the inflammatory injury induced by T. pyogenes, and suggests that blocking NLR or TNF- may be a potential therapeutic strategy against T. pyogenes infection.

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Qin, L., Meng, F., He, H., Li, S., Zhang, H., Sun, Y., Zhang, W., An, T.-Q., Cai, X., Wang, S.. 2023-07-26. Inflammation plays a critical role in damage to the bronchiolar epithelium induced by Trueperella pyogenes in vitro and in vivo. https://doi.org/10.1101/2023.07.24.550341

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