Zschaler Josefin, Schlorke Denise, Arnhold Juergen
Translational Centre for Regenerative Medicine (TRM); Institute for Medical Physics and Biophysics, Medical Faculty, Leipzig University, Leipzig, Germany.
Crit Rev Immunol. 2014;34(5):433-54.
Mouse strains are frequently used to model human disease states, to test the efficiency of drugs and therapeutic principles. However, the direct translation of murine experimental data to human pathological events often fails due to sufficient differences in the organization of the immune system of both species. Here we give a short overview of the principle differences between mice and humans in defense strategies against pathogens and mechanisms involved in response to pathogenic microorganisms and other activators of the immune system. While in human blood mechanisms of immune resistance are highly prevailed, tolerance mechanisms dominate for the defense against pathogenic microorganisms in mouse blood. Further on, species-related differences of immune cells mainly involved in innate immune response as well as differences to maintain oxidative homeostasis are also considered. A number of disease scenarios in mice are critically reflected for their suitability to serve as a model for human pathologies. Due to setbacks in these studies, novel mouse models were created to bridge the immune system of both species: humanized mice. Accordingly, a special section of this review is devoted to new results applying humanized mouse models taking limitations and prospects into account.
小鼠品系经常被用于模拟人类疾病状态,以测试药物的疗效和治疗原理。然而,由于这两个物种免疫系统组织存在足够差异,将小鼠实验数据直接转化为人类病理事件往往会失败。在此,我们简要概述小鼠和人类在抵御病原体的防御策略以及对致病微生物和免疫系统其他激活剂的反应机制方面的主要差异。在人类血液中,免疫抵抗机制占主导地位,而在小鼠血液中,耐受机制在抵御致病微生物方面占主导地位。此外,还考虑了主要参与先天免疫反应的免疫细胞的物种相关差异以及维持氧化稳态的差异。对小鼠中的一些疾病情况作为人类病理学模型的适用性进行了批判性反思。由于这些研究中的挫折,人们创建了新的小鼠模型来弥合这两个物种的免疫系统差异:人源化小鼠。因此,本综述的一个特别部分专门介绍了考虑到局限性和前景应用人源化小鼠模型的新结果。