Insects as Models for Studying the Virulence of Fungal Pathogens of Humans

Abstract

Vertebrates such as birds, rabbits, guinea pigs, and rodents (Clemons & Stevens, 2005), have been employed extensively over a long period of time to study various aspects of microbial pathogenesis, innate and acquired immune responses, disease transmission, and therapy. However, these models are extremely costly to use and, in many cases, their use is no longer considered to be ethically acceptable. There is a critical requirement to develop and validate alternative models for studying microbial pathogenesis and recent studies have highlighted the use of a variety of invertebrates as models for studying microbial virulence and the efficacy of antimicrobial drugs (for reviews see: Kavanagh & Reeves, 2004; Scully & Bidochka, 2006). Due to the strong structural and functional similarities between the immune response of insects and the innate immune response of mammals, the study of microbial virulence and of the efficacy of novel antimicrobial drugs has recently begun to utilise insects in order to model the innate immune response of mammals. Insects represent one of the most successful groups of animals, exploiting almost all niches on Earth, except the seas, and accounting for at least 1 million species and 10 individuals (Vilmos & Kurucz, 1998). Insects diverged from vertebrates approximately 500 million years ago and despite this early divergence, have maintained an immune response with strong structural and functional similarities to the innate immune response of mammals (Vilmos & Kurucz, 1998; Salzet, 2001). Insects rely exclusively upon an immune system analogous to the innate immune response of mammals and consequently have become extremely valuable as models for studying vertebrate innate immune responses to many pathogenic micro-organsims. In vertebrates the different aspects of the innate and adaptive immune responses intertwine, connect and overlap. For example, interleukin-12 (IL-12), an antiinflammatory cytokine that acts as an immunological messenger, is produced and secreted by macrophages during an immune response. IL-12 activates T cells, which in turn activate other cells involved in the immune response. In order to investigate those responses that are solely components of the innate immune response, employing an invertebrate model such as an insect that relies exclusively on an innate immune response, is advantageous. It is also becoming increasingly