Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Janssen Research and Development, Spring House, Pennsylvania, USA.
J Invest Dermatol. 2020 Aug;140(8):1488-1497.e1. doi: 10.1016/j.jid.2020.04.012. Epub 2020 May 11.
Bacterial skin infections are a major societal health burden and are increasingly difficult to treat owing to the emergence of antibiotic-resistant strains such as community-acquired methicillin-resistant Staphylococcus aureus. Understanding the immunologic mechanisms that provide durable protection against skin infections has the potential to guide the development of immunotherapies and vaccines to engage the host immune response to combat these antibiotic-resistant strains. To this end, mouse skin infection models allow researchers to examine host immunity by investigating the timing, inoculum, route of infection and the causative bacterial species in different wild-type mouse backgrounds as well as in knockout, transgenic, and other types of genetically engineered mouse strains. To recapitulate the various types of human skin infections, many different mouse models have been developed. For example, four models frequently used in dermatological research are based on the route of infection, including (i) subcutaneous infection models, (ii) intradermal infection models, (iii) wound infection models, and (iv) epicutaneous infection models. In this article, we will describe these skin infection models in detail along with their advantages and limitations. In addition, we will discuss how humanized mouse models such as the human skin xenograft on immunocompromised mice might be used in bacterial skin infection research.
细菌皮肤感染是一个重大的社会健康负担,由于出现了耐抗生素的菌株,如社区获得性耐甲氧西林金黄色葡萄球菌,治疗难度越来越大。了解提供持久皮肤感染保护的免疫机制有可能指导免疫疗法和疫苗的开发,以利用宿主的免疫反应来对抗这些耐抗生素的菌株。为此,小鼠皮肤感染模型允许研究人员通过研究不同野生型小鼠背景下以及敲除、转基因和其他类型的基因工程小鼠品系中感染的时间、接种物、感染途径和致病细菌种类,来检查宿主的免疫。为了再现各种类型的人类皮肤感染,已经开发了许多不同的小鼠模型。例如,在皮肤病学研究中经常使用的四种模型是基于感染途径的,包括(i)皮下感染模型,(ii)皮内感染模型,(iii)伤口感染模型,和(iv)表皮感染模型。在本文中,我们将详细描述这些皮肤感染模型及其优缺点。此外,我们还将讨论如何在细菌皮肤感染研究中使用人源化小鼠模型,如免疫缺陷小鼠上的人皮肤异种移植物。