PMID- 37929972 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20231216 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 91 IP - 12 DP - 2023 Dec 12 TI - Inflammation plays a critical role in damage to the bronchiolar epithelium induced by Trueperella pyogenes in vitro and in vivo. PG - e0027323 LID - 10.1128/iai.00273-23 [doi] LID - e00273-23 AB - 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. FAU - Qin, Lei AU - Qin L AD - State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China. AD - Laboratory Animal Centre, Qiqihar Medical University, Qiqihar, China. FAU - Meng, Fandan AU - Meng F AD - State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China. FAU - He, Haijuan AU - He H AD - Institute of Animal Husbandry, Heilongjiang Academy of Agriculture Sciences, Harbin, Heilongjiang, China. FAU - Li, Siqi AU - Li S AD - State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China. FAU - Zhang, Hongliang AU - Zhang H AD - State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China. FAU - Sun, Yuan AU - Sun Y AD - State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China. FAU - Zhang, Wenlong AU - Zhang W AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, China. FAU - An, Tongqing AU - An T AUID- ORCID: 0000-0003-4619-4587 AD - State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China. FAU - Cai, Xuehui AU - Cai X AUID- ORCID: 0000-0001-9098-7782 AD - State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China. AD - Heilongjiang Research Center for Veterinary Biopharmaceutical Technology, Harbin, China. FAU - Wang, Shujie AU - Wang S AUID- ORCID: 0000-0002-7020-5410 AD - State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China. AD - Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin, China. LA - eng GR - 32273018/MOST | National Natural Science Foundation of China (NSFC)/ GR - NO.1610302022006/Central Public-interest Scientific Institution Basal Research Fund/ GR - LH2023C048/Heilongjiang Provincial Natural Science Foundation of China/ GR - 2018-KYYWF-0109/Foundation of Heilongjiang Educational Committee/ PT - Journal Article DEP - 20231106 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Cytokines) SB - IM MH - Animals MH - Mice MH - Swine MH - *Proto-Oncogene Proteins c-akt MH - *Tumor Necrosis Factor-alpha MH - Inflammation MH - Epithelium/pathology MH - Cytokines PMC - PMC10714949 OTO - NOTNLM OT - PBECs OT - PCLS OT - Trueperella pyogenes OT - infection OT - inflammation OT - intracellular pathways COIS- The authors declare no conflict of interest. EDAT- 2023/11/06 12:43 MHDA- 2023/12/17 09:44 PMCR- 2023/11/06 CRDT- 2023/11/06 08:04 PHST- 2023/12/17 09:44 [medline] PHST- 2023/11/06 12:43 [pubmed] PHST- 2023/11/06 08:04 [entrez] PHST- 2023/11/06 00:00 [pmc-release] AID - 00273-23 [pii] AID - iai.00273-23 [pii] AID - 10.1128/iai.00273-23 [doi] PST - ppublish SO - Infect Immun. 2023 Dec 12;91(12):e0027323. doi: 10.1128/iai.00273-23. Epub 2023 Nov 6.