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

Infect Immun.2023 Nov 6:e0027323.doi: 10.1128/iai.00273-23. Online ahead of print.

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 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-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  T. pyogenes  and suggests that blocking NLR may be a potential therapeutic strategy against  T. pyogenes  infection.

Keywords: PBECs; PCLS; Trueperella pyogenes; infection; inflammation; intracellular pathways.