呼吸道感染(RTI)是人类发病和死亡的主要原因。大量的RTI是由病毒引起的,通常会导致婴儿更严重的疾病,老年人和免疫功能低下的人。病毒感染后,大多数个体经历与上RTI相关的普通感冒样症状。然而,在某些情况下,可能会出现严重的,有时危及生命的较低RTI。为了研究呼吸道病毒与宿主之间的相互作用,需要能够准确反映人类呼吸道的可复制和可扩展的体外培养模型,并测试新的治疗干预措施。已经描述了多种体外呼吸细胞培养系统,但其中大多数是基于永生化的细胞系。虽然有助于研究病毒感染的某些方面,这样的单态,单细胞系统在创建在整合组织水平上发生的过程的理解方面不足。涉及原代人气道上皮细胞的新型体外模型,最近,人类气道类器官,现在正在使用。在这次审查中,我们描述了在病毒RTI的背景下,体外细胞培养系统的进化及其特征,从永生化细胞培养物到最近开发的类器官系统的发展开始。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,向性和受体研究以及与先天免疫系统的相互作用。最后,我们为这一领域的未来发展提供了展望,包括模拟呼吸道微环境的辅因子。
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 in vitro 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 in vitro 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 in vitro 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 in vitro 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.