McDonald Katya, Rodriguez Adryiana, Muthukrishnan Gowrishankar
Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA.
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Antibiotics (Basel). 2024 Jul 11;13(7):640. doi: 10.3390/antibiotics13070640.
Bacterial infections continue to represent a significant healthcare burden worldwide, causing considerable mortality and morbidity every year. The emergence of multidrug-resistant bacterial strains continues to rise, posing serious risks to controlling global disease outbreaks. To develop novel and more effective treatment and vaccination programs, there is a need for clinically relevant small animal models. Since multiple bacterial species have human-specific tropism for numerous virulence factors and toxins, conventional mouse models do not fully represent human disease. Several human disease characteristic phenotypes, such as lung granulomas in the case of infections, are absent in standard mouse models. Alternatively, certain pathogens, such as serovar and , can be well tolerated in mice and cleared quickly. To address this, multiple groups have developed humanized mouse models and observed enhanced susceptibility to infection and a more faithful recapitulation of human disease. In the last two decades, multiple humanized mouse models have been developed to attempt to recapitulate the human immune system in a small animal model. In this review, we first discuss the history of immunodeficient mice that has enabled the engraftment of human tissue and the engraftment methods currently used in the field. We then highlight how humanized mouse models successfully uncovered critical human immune responses to various bacterial infections, including , , and .
细菌感染在全球范围内仍然是一个重大的医疗负担，每年都会导致相当高的死亡率和发病率。多重耐药细菌菌株的出现持续增加，给控制全球疾病爆发带来严重风险。为了开发新颖且更有效的治疗和疫苗接种方案，需要具有临床相关性的小动物模型。由于多种细菌物种对众多毒力因子和毒素具有人类特异性嗜性，传统的小鼠模型不能完全代表人类疾病。一些人类疾病特征性表型，如感染时的肺部肉芽肿，在标准小鼠模型中并不存在。或者，某些病原体，如血清型和，可以在小鼠中很好地耐受并迅速清除。为了解决这个问题，多个研究小组开发了人源化小鼠模型，并观察到其对感染的易感性增强以及对人类疾病的更真实模拟。在过去的二十年中，已经开发了多种人源化小鼠模型，试图在小动物模型中重现人类免疫系统。在这篇综述中，我们首先讨论了使人类组织能够植入的免疫缺陷小鼠的历史以及该领域目前使用的植入方法。然后，我们重点介绍人源化小鼠模型如何成功揭示了人类对各种细菌感染（包括、和）的关键免疫反应。
