Abstract：
Traditionally, molecular mechanisms of pathogenesis for infectious agents were studied in cell culture or animal models but have limitations on the extent to which the resulting data reflect natural infection in humans. The COVID-19 pandemic has highlighted the urgent need to rapidly develop laboratory models that enable the study of host-pathogen interactions, particularly the relative efficacy of preventive measures. Recently, human and animal ex vivo tissue challenge models have emerged as a promising avenue to study immune responses, screen potential therapies and triage vaccine candidates. This approach offers the opportunity to closely approximate human disease from the perspective of pathology and immune response. It has advantages compared to animal models which are expensive, lengthy and often require containment facilities. Herein, we summarize some recent advances in the development of ex vivo tissue challenge models for COVID-19, HIV-1 and other pathogens. We focus on the contribution of these models to enhancing knowledge of host-pathogen interactions, immune modulation, and their value in testing therapeutic agents. We further highlight the advantages and limitations of using ex vivo challenge models and briefly summarize how the use of organoids provides a useful advancement over current approaches. Collectively, these developments have enormous potential for the study of infectious diseases.
摘要：
传统上,在细胞培养或动物模型中研究了感染因子发病机理的分子机制，但在所得数据反映人类自然感染的程度上存在局限性。COVID-19大流行凸显了迫切需要快速开发实验室模型，以研究宿主-病原体相互作用，特别是预防措施的相对有效性。最近,人和动物离体组织攻击模型已成为研究免疫反应的有希望的途径，筛选潜在的疗法和分诊候选疫苗。这种方法提供了从病理学和免疫应答的角度密切近似人类疾病的机会。与昂贵的动物模型相比，它具有优势，冗长，通常需要收容设施。在这里，我们总结了COVID-19，HIV-1和其他病原体的离体组织攻击模型开发的一些最新进展。我们专注于这些模型对增强宿主-病原体相互作用知识的贡献，免疫调节，以及它们在测试治疗剂方面的价值。我们进一步强调了使用离体挑战模型的优点和局限性，并简要总结了使用类器官如何比当前方法提供了有用的进步。总的来说，这些发展对于传染病的研究具有巨大的潜力。
