Premachandre Chintha K, Quah Pin Shie, Tran Bang Manh, Vincan Elizabeth, Deliyannis Georgia, Wong Chinn Yi, Diaz-Méndez Andrés, Jackson David C, Reading Patrick C, Browning Glenn F, Vaz Paola K, Wawegama Nadeeka K
Asia-Pacific Centre for Animal Health, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, Victoria 3010, Australia.
Department of Microbiology and Immunology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
Vet Microbiol. 2025 Jan;300:110340. doi: 10.1016/j.vetmic.2024.110340. Epub 2024 Dec 10.
In vitro three-dimensional organoid models simulate key aspects of the structure and function of in vivo organs and have been used to study physiology, host-pathogen interactions, pathogenesis and pharmacodynamics. Although most organoid studies have been developed using human or mouse tissues, recent advancements have enabled the establishment of intestinal and respiratory tract organoids from domestic animal samples. Mycoplasma bovis causes chronic respiratory tract infections in cattle with significant health and economic consequences. The pathogenesis and virulence factors of M. bovis have been studied in several in vitro infection models, but the use of organoids has not been examined previously. In this study, we assessed the feasibility of using a matrix-embedded bovine tracheal organoid system to study respiratory infections with M. bovis. Bovine tracheal organoids were inoculated with M. bovis strain MbovMil and incubated for 72 hours to investigate the ability of M. bovis to proliferate, attach and invade the organoids. M. bovis was able to infect the organoids, resulting in a mean 260-fold increase in the titre of viable M. bovis by 72 hours post-inoculation. Examination of the infected organoids using transmission electron microscopy revealed the presence of mycoplasmas within the organoid cells and membrane bound clusters of M. bovis inside the intercellular junctions. Our findings indicate that bovine tracheal organoids can be used as a model system for studying respiratory tract infections caused by M. bovis.
体外三维类器官模型模拟体内器官结构和功能的关键方面,已被用于研究生理学、宿主-病原体相互作用、发病机制和药效学。尽管大多数类器官研究是使用人类或小鼠组织开展的,但最近的进展使得能够从家畜样本中建立肠道和呼吸道类器官。牛支原体可导致牛的慢性呼吸道感染,造成重大的健康和经济后果。牛支原体的发病机制和毒力因子已在几种体外感染模型中进行了研究,但此前尚未研究过类器官的应用。在本研究中,我们评估了使用基质包埋的牛气管类器官系统研究牛支原体呼吸道感染的可行性。用牛支原体菌株MbovMil接种牛气管类器官,并孵育72小时,以研究牛支原体增殖、附着和侵入类器官的能力。牛支原体能够感染类器官,在接种后72小时,活牛支原体滴度平均增加260倍。使用透射电子显微镜检查感染的类器官,发现类器官细胞内存在支原体,细胞间连接处有膜结合的牛支原体簇。我们的研究结果表明,牛气管类器官可作为研究牛支原体引起的呼吸道感染的模型系统。