Innate Immunity Unit, Immunology Department, Institut Pasteur, Paris, France.
Inserm U1223, Paris, France.
Microbiol Spectr. 2019 Mar;7(2). doi: 10.1128/microbiolspec.BAI-0019-2019.
Human immune system (HIS) mice are created by transplanting human immune cells or their progenitor cells into highly immunodeficient recipient mouse hosts, thereby "humanizing" their immune systems. Over past decades, the field of HIS mice has evolved rapidly, as modifications of existing immunodeficient mouse strains have been developed, resulting in increasing levels of human tissue engraftment as humanization is optimized. Current HIS mouse models not only permit elevated levels of human cell engraftment but also demonstrate graft stability. As such, HIS mice are being extensively used to study the human innate and adaptive immune response against microbial infections . Compared to nonhumanized animal models, which are frequently infected with surrogate or adapted microbes, the HIS mouse models allow the analysis of interactions between human immune cells and pathogenic microbes, making them a more clinically relevant model. This article reviews the development of HIS mice and covers the different strategies used to humanize mice, as well as discussing the use of HIS mice for studying bacterial infections that cause human disease.
人免疫系统(HIS)小鼠通过将人类免疫细胞或其祖细胞移植到高度免疫缺陷的受体小鼠宿主中而构建,从而“人源化”其免疫系统。在过去的几十年中,HIS 小鼠领域发展迅速,因为现有的免疫缺陷小鼠品系经过修饰,从而实现了更高水平的人组织移植,进而优化了人源化。目前的 HIS 小鼠模型不仅允许高水平的人细胞移植,而且还显示出移植物的稳定性。因此,HIS 小鼠被广泛用于研究人类先天和适应性免疫对微生物感染的反应。与经常感染替代或适应微生物的非人源化动物模型相比,HIS 小鼠模型允许分析人类免疫细胞与致病性微生物之间的相互作用,使其成为更具临床相关性的模型。本文综述了 HIS 小鼠的发展,并介绍了用于人源化小鼠的不同策略,同时讨论了 HIS 小鼠在研究导致人类疾病的细菌感染中的应用。