The contribution of animal models of aspergillosis to understanding pathogenesis, therapy and virulence

Abstract

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.