Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.
Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Ticks Tick Borne Dis. 2020 Nov;11(6):101538. doi: 10.1016/j.ttbdis.2020.101538. Epub 2020 Aug 7.
The guinea pig (Cavia porcellus) has an established track record as an animal model, with its utility in rickettsial research documented as early as the turn of the 20 century. From identifying Rickettsia rickettsii as the agent of Rocky Mountain spotted fever and ticks as the natural transmission route to evaluating protective immunity and treatment for tick-borne rickettsiae, guinea pigs have been essential for advances in our understanding of spotted fever rickettsioses (SFR). Tick feeding on guinea pigs is feasible and results in transmission of tick-borne rickettsiae. The resulting infection leads to the recapitulation of SFR as defined by clinical signs that include fever, unthrift, and in the case of transmission by a Rickettsia parkeri-infected Amblyomma maculatum tick, a characteristic eschar at the site of the bite. No other small animal model recapitulates SFR, is large enough to collect multiple blood and skin samples for longitudinal studies, and has an immune system as similar to the human immune system. In the 1980s, the use of the guinea pig was significantly reduced due to advances made to the more reproductively prolific and inexpensive murine model. These advances included the development of genetically modified murine strains, which resulted in the expansion of murine-specific reagents and assays. Still, the advantages of the guinea pig as a model for SFR persist, novel assays are being developed to better monitor guinea pig immune responses, and tools, like CRISPR/Cas9, are now available. These technical advances allow guinea pigs to again contribute to our understanding of SFR. Importantly, returning to the guinea pig model with enhanced tools will enable rickettsial researchers to corroborate and potentially refine results acquired using mice. This minireview summarizes Cavia porcellus as an animal model for human tick-borne rickettsial diseases.
豚鼠（Cavia porcellus）作为一种动物模型具有成熟的应用记录，早在 20 世纪初，其在立克次体研究中的作用就已得到证实。从鉴定落矶山斑点热的病原体为立氏立克次体（Rickettsia rickettsii）以及蜱为天然传播途径，到评估针对蜱传立克次体的保护性免疫和治疗方法，豚鼠在我们对斑点热立克次体病（spotted fever rickettsioses，SFR）的理解方面发挥了重要作用。豚鼠可被蜱叮咬并传播蜱传立克次体。感染后会出现 SFR 的临床症状，包括发热、消瘦，在由感染立氏立克次体的柏氏禽刺螨（Amblyomma maculatum）传播的情况下，在叮咬部位还会出现特征性焦痂。没有其他小型动物模型可以重现 SFR，也没有足够大的动物模型能够收集多个血液和皮肤样本进行纵向研究，并且没有与人类免疫系统如此相似的动物模型。20 世纪 80 年代，由于在更具繁殖力且成本更低的鼠类模型方面取得的进展，豚鼠的使用明显减少。这些进展包括遗传修饰鼠种的开发，从而扩大了鼠特异性试剂和检测方法的应用。尽管如此，豚鼠作为 SFR 模型的优势仍然存在，新的检测方法正在开发以更好地监测豚鼠的免疫反应，并且像 CRISPR/Cas9 这样的工具也已经可用。这些技术进步使豚鼠再次为我们理解 SFR 做出贡献。重要的是，利用增强型工具重新采用豚鼠模型将使立克次体研究人员能够证实并可能改进使用鼠类模型获得的结果。本文综述了豚鼠作为人类蜱传立克次体病的动物模型。
