Clemons K V, Stevens D A
California Institute for Medical Research, San Jose, CA 95128, USA.
Med Mycol. 2005 May;43 Suppl 1:S101-10. doi: 10.1080/13693780500051919.
Animal models of aspergillosis have been used extensively to study various aspects of pathogenesis, innate and acquired host-response, disease transmission and therapy. Several different animal models of aspergillosis have been developed. Because aspergillosis is an important pulmonary disease in birds, avian models have been used successfully to study preventative vaccines. Studies done to emulate human disease have relied on models using common laboratory animal species. Guinea pig models have primarily been used in therapy studies of invasive pulmonary aspergillosis (IPA). Rabbits have been used to study IPA and systemic disease, as well as fungal keratitis. Rodent, particularly mouse, models of aspergillosis predominate as the choice for most investigators. The availability of genetically defined strains of mice, immunological reagents, cost and ease of handling are factors. Both normal and immunosuppressed animals are used routinely. These models have been used to determine efficacy of experimental therapeutics, comparative virulence of different isolates of Aspergillus, genes involved in virulence, and susceptibility to infection with Aspergillus. Mice with genetic immunological deficiency and cytokine gene-specific knockout mice facilitate studies of the roles cells, and cytokines and chemokines, play in host-resistance to Aspergillus. Overall, these models have been critical to the advancement of therapy, and our current understanding of pathogenesis and host-resistance.
曲霉病动物模型已被广泛用于研究发病机制、先天性和获得性宿主反应、疾病传播及治疗等各个方面。现已开发出几种不同的曲霉病动物模型。由于曲霉病在鸟类中是一种重要的肺部疾病,禽类模型已成功用于研究预防性疫苗。为模拟人类疾病所开展的研究依赖于使用常见实验动物物种的模型。豚鼠模型主要用于侵袭性肺曲霉病(IPA)的治疗研究。兔子已被用于研究IPA和全身性疾病,以及真菌性角膜炎。啮齿动物,尤其是小鼠,曲霉病模型是大多数研究者的首选。小鼠基因定义品系的可获得性、免疫试剂、成本及易于操作都是考虑因素。正常和免疫抑制动物都常规使用。这些模型已被用于确定实验性治疗的疗效、不同曲霉分离株的相对毒力、与毒力相关的基因以及对曲霉感染的易感性。具有遗传免疫缺陷的小鼠和细胞因子基因特异性敲除小鼠有助于研究细胞、细胞因子和趋化因子在宿主对曲霉抵抗力中所起的作用。总体而言,这些模型对于治疗的进展以及我们目前对发病机制和宿主抵抗力的理解至关重要。