Rijsbergen Laurine C, van Dijk Laura L A, Engel Maarten F M, de Vries Rory D, de Swart Rik L
Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.
Medical Library, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.
Front Immunol. 2021 Aug 18;12:683002. doi: 10.3389/fimmu.2021.683002. eCollection 2021.
Respiratory tract infections (RTI) are a major cause of morbidity and mortality in humans. A large number of RTIs is caused by viruses, often resulting in more severe disease in infants, elderly and the immunocompromised. Upon viral infection, most individuals experience common cold-like symptoms associated with an upper RTI. However, in some cases a severe and sometimes life-threatening lower RTI may develop. Reproducible and scalable culture models that accurately reflect the human respiratory tract are needed to study interactions between respiratory viruses and the host, and to test novel therapeutic interventions. Multiple respiratory cell culture systems have been described, but the majority of these are based on immortalized cell lines. Although useful for studying certain aspects of viral infections, such monomorphic, unicellular systems fall short in creating an understanding of the processes that occur at an integrated tissue level. Novel models involving primary human airway epithelial cells and, more recently, human airway organoids, are now in use. In this review, we describe the evolution of cell culture systems and their characteristics in the context of viral RTIs, starting from advances after immortalized cell cultures to more recently developed organoid systems. Furthermore, we describe how these models are used in studying virus-host interactions, e.g. tropism and receptor studies as well as interactions with the innate immune system. Finally, we provide an outlook for future developments in this field, including co-factors that mimic the microenvironment in the respiratory tract.
呼吸道感染（RTI）是人类发病和死亡的主要原因。大量的呼吸道感染由病毒引起，常常在婴儿、老年人和免疫功能低下者中导致更严重的疾病。病毒感染后，大多数人会出现与上呼吸道感染相关的类似普通感冒的症状。然而，在某些情况下，可能会发展为严重的、有时甚至危及生命的下呼吸道感染。需要能够准确反映人类呼吸道的可重复且可扩展的培养模型，以研究呼吸道病毒与宿主之间的相互作用，并测试新型治疗干预措施。已经描述了多种呼吸道细胞培养系统，但其中大多数基于永生化细胞系。尽管这些系统对于研究病毒感染的某些方面很有用，但这种单形的单细胞系统在理解整合组织水平上发生的过程方面存在不足。现在正在使用涉及原代人呼吸道上皮细胞以及最近的人呼吸道类器官的新型模型。在这篇综述中，我们描述了细胞培养系统在病毒引起的呼吸道感染背景下的演变及其特征，从永生化细胞培养后的进展到最近开发的类器官系统。此外，我们描述了这些模型如何用于研究病毒 - 宿主相互作用，例如嗜性和受体研究以及与先天免疫系统的相互作用。最后，我们展望了该领域的未来发展，包括模拟呼吸道微环境的辅助因子。
