Division of Molecular Thoracic Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.
J Virol. 2022 Apr 13;96(7):e0009822. doi: 10.1128/jvi.00098-22. Epub 2022 Mar 14.
Respiratory viruses cause mild to severe diseases in humans every year, constituting a major public health problem. Characterizing the pathogenesis in physiologically relevant models is crucial for developing efficient vaccines and therapeutics. Here, we show that lung organoids derived from human primary or lung tumor tissue maintain the cellular composition and characteristics of the original tissue. Moreover, we show that these organoids sustain viral replication with particular infection foci formation, and they activate the expression of interferon-associated and proinflammatory genes responsible for mediating a robust innate immune response. All together, we show that three-dimensional (3D) lung organoids constitute a relevant platform to model diseases and enable the development of drug screenings. Three-dimensional (3D) human lung organoids reflect the native cell composition of the lung as well as its physiological properties. Human 3D lung organoids offer ideal conditions, such as timely availability in large quantities and high physiological relevance for reassessment and prediction of disease outbreaks of respiratory pathogens and pathogens that use the lung as a primary entry portal. Human lung organoids can be used in basic research and diagnostic settings as early warning cell culture systems and also serve as a relevant platform for modeling infectious diseases and drug development. They can be used to characterize pathogens and analyze the influence of infection on, for example, immunological parameters, such as the expression of interferon-associated and proinflammatory genes in the context of cancer. In our study, we found that cancer-derived lung organoids were more sensitive to influenza A virus infection than those derived from healthy tissue and demonstrated a decreased innate immune response.
呼吸道病毒每年都会导致人类患轻度至重度疾病，这构成了一个主要的公共卫生问题。在生理相关模型中阐明发病机制对于开发有效的疫苗和疗法至关重要。在这里，我们表明源自人原代或肺肿瘤组织的肺类器官保持了原始组织的细胞组成和特征。此外，我们表明这些类器官可以维持病毒复制，并形成特定的感染焦点，同时它们激活了干扰素相关和促炎基因的表达，这些基因负责介导强大的先天免疫反应。总之，我们表明三维（3D）肺类器官构成了一种相关的平台，可以模拟疾病，并能够开发药物筛选。 三维（3D）人肺类器官反映了肺的天然细胞组成及其生理特性。人 3D 肺类器官提供了理想的条件，例如及时大量供应和高度生理相关性，可重新评估和预测呼吸道病原体和以肺为主要进入门户的病原体的疾病爆发。人肺类器官可用于基础研究和诊断环境，作为早期预警细胞培养系统，也可作为用于模拟传染病和药物开发的相关平台。它们可用于表征病原体，并分析感染对例如干扰素相关和促炎基因表达等免疫参数的影响，这在癌症背景下尤其重要。在我们的研究中，我们发现源自癌症的肺类器官比源自健康组织的肺类器官对甲型流感病毒感染更为敏感，并表现出先天免疫反应的降低。
