人源化小鼠模型是研究人类免疫系统对感染和损伤的反应的宝贵工具。我们之前描述过通过输注来自脐带的人类白细胞抗原 (HLA) 匹配的人类造血干细胞产生的人类免疫系统 (HIS)-DRAGA 小鼠 (HLA-A2.HLA-DR4.Rag1KO.IL-2RgKO.NOD)脐带血。通过重建人类细胞，HIS-DRAGA小鼠模型已被用作人类免疫缺陷病毒（HIV）、流感、2019年冠状病毒病（COVID-19）、恙虫病和斑疹伤寒等传染病的“替代体内人类模型”。疟疾。这种人源化小鼠模型绕过了使用胎儿组织进行实验动物人源化的伦理担忧。在这里，我们证明了 HIS-DRAGA 小鼠大脑中存在人类小胶质细胞和 T 细胞。小胶质细胞是大脑驻留的巨噬细胞，在对抗病原体和脑损伤方面发挥着关键作用，而大脑驻留的 T 细胞则负责监视和防御感染。我们的研究结果表明，HIS-DRAGA 小鼠模型为研究感染、退行性疾病、肿瘤和创伤期间大脑中人类小胶质细胞和 T 细胞的功能以及测试这些病理条件下的治疗方法提供了独特的优势。版权所有 © 2024 年戈什·罗伊、卡里姆、布鲁梅努和卡萨雷斯。

Humanized mouse models are valuable tools for investigating the human immune system in response to infection and injury. We have previously described the human immune system (HIS)-DRAGA mice (HLA-A2.HLA-DR4.Rag1KO.IL-2RgKO.NOD) generated by infusion of Human Leukocyte Antigen (HLA)-matched, human hematopoietic stem cells from umbilical cord blood. By reconstituting human cells, the HIS-DRAGA mouse model has been utilized as a "surrogate in vivo human model" for infectious diseases such as Human Immunodeficiency Virus (HIV), Influenza, Coronavirus Disease 2019 (COVID-19), scrub typhus, and malaria. This humanized mouse model bypasses ethical concerns about the use of fetal tissues for the humanization of laboratory animals. Here in, we demonstrate the presence of human microglia and T cells in the brain of HIS-DRAGA mice. Microglia are brain-resident macrophages that play pivotal roles against pathogens and cerebral damage, whereas the brain-resident T cells provide surveillance and defense against infections. Our findings suggest that the HIS-DRAGA mouse model offers unique advantages for studying the functions of human microglia and T cells in the brain during infections, degenerative disorders, tumors, and trauma, as well as for testing therapeutics in these pathological conditions.Copyright © 2024 Ghosh Roy, Karim, Brumeanu and Casares.