Research Center of Swine Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, New York, New York, USA.
Infect Immun. 2023 Dec 12;91(12):e0035123. doi: 10.1128/iai.00351-23. Epub 2023 Nov 6.
Virulent may engender systemic infection characterized by fibrinous polyserositis and pneumonia. causes systemic disease through upper respiratory tract infection, but the mechanism has not been fully characterized. Tight junction (TJ) proteins maintain the integrity and impermeability of the epithelial barriers. In this work, we applied the recombinant cytolethal distending toxin (CDT) holotoxin and -deficient mutants to assess whether CDT interacted with TJ proteins of airway tract cells. Our results indicated that CDT induced the TJ occludin (OCLN) expression in newborn pig tracheal epithelial cells within the first 3 hours of bacterial infection, followed by a significant decrease. Overexpression of OCLN in target cells made them more susceptible to adhesion, whereas ablation of OCLN expression by CRISPR/Cas 9 gene editing technology in target cells decreased their susceptibility to bacterial adhesion. In addition, CDT treatment could upregulate the OCLN levels in the lung tissue of C57/BL6 mice. In summary, highly virulent strain SC1401 stimulated the tight junction expression, resulting in higher bacterial adhesion to respiratory tract cells, and this process is closely related to CDT. Our results may provide novel insights into infection and CDT-mediated pathogenesis.
产毒株可能引发以纤维蛋白性多发性浆膜炎和肺炎为特征的全身感染。通过上呼吸道感染引起全身疾病，但机制尚未完全阐明。紧密连接（TJ）蛋白维持上皮屏障的完整性和通透性。在这项工作中，我们应用重组细胞致死膨胀毒素（CDT）全毒素和 -缺陷突变体来评估 CDT 是否与气道细胞的 TJ 蛋白相互作用。我们的结果表明，CDT 在细菌感染后的前 3 小时内诱导新生猪气管上皮细胞中 TJ 紧密连接蛋白（OCLN）的表达，随后显著下降。靶细胞中 OCLN 的过表达使它们更容易被 粘附，而 CRISPR/Cas9 基因编辑技术敲除靶细胞中的 OCLN 表达则降低了它们对细菌粘附的易感性。此外，CDT 处理可上调 C57/BL6 小鼠肺组织中的 OCLN 水平。总之，高毒力 菌株 SC1401 刺激紧密连接表达，导致呼吸道细胞对细菌的粘附增加，这一过程与 CDT 密切相关。我们的研究结果可能为 感染和 CDT 介导的发病机制提供新的见解。
