Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
Sci Rep. 2024 May 20;14(1):11479. doi: 10.1038/s41598-024-62407-2.
Salmonella enterica serovar Dublin (S. Dublin) is an important enteric pathogen affecting cattle and poses increasing public health risks. Understanding the pathophysiology and host-pathogen interactions of S. Dublin infection are critical for developing effective control strategies, yet studies are hindered by the lack of physiologically relevant in vitro models. This study aimed to generate a robust ileal monolayer derived from adult bovine organoids, validate its feasibility as an in vitro infection model with S. Dublin, and evaluate the epithelial response to infection. A stable, confluent monolayer with a functional epithelial barrier was established under optimized culture conditions. The model's applicability for studying S. Dublin infection was confirmed by documenting intracellular bacterial invasion and replication, impacts on epithelial integrity, and a specific inflammatory response, providing insights into the pathogen-epithelium interactions. The study underscores the utility of organoid-derived monolayers in advancing our understanding of enteric infections in livestock and highlights implications for therapeutic strategy development and preventive measures, with potential applications extending to both veterinary and human medicine. The established bovine ileal monolayer offers a novel and physiologically relevant in vitro platform for investigating enteric pathogen-host interactions, particularly for pathogens like S. Dublin.
都柏林沙门氏菌(S. Dublin)是一种重要的肠道病原体,影响牛并对公共健康构成越来越大的风险。了解 S. Dublin 感染的病理生理学和宿主-病原体相互作用对于制定有效的控制策略至关重要,但由于缺乏生理相关的体外模型,研究受到阻碍。本研究旨在从成年牛类器官中生成稳健的回肠单层,并验证其作为 S. Dublin 体外感染模型的可行性,以及评估上皮细胞对感染的反应。在优化的培养条件下,建立了稳定、融合的具有功能性上皮屏障的单层。通过记录细胞内细菌入侵和复制、对上皮完整性的影响以及特定的炎症反应,证实了该模型在研究 S. Dublin 感染方面的适用性,从而深入了解病原体-上皮相互作用。该研究强调了类器官衍生的单层在推进对家畜肠道感染的理解方面的实用性,并突出了其对治疗策略开发和预防措施的意义,潜在应用扩展到兽医和人类医学。所建立的牛回肠单层为研究肠道病原体-宿主相互作用提供了新颖且生理相关的体外平台,特别是对于 S. Dublin 等病原体。