Insect Models for Studying Microbial Pathogens of Mammals

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 1018 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 anti-inflammatory 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

K. Kavanagh (ed.), New Insights in Medical Mycology. © Springer 2007

clear that the innate immune response, the first line of defence against invading microbes, is indispensable in fighting many infections. Individuals suffering from neutropenia, caused by reduced quantities of circulating neutrophils, or chronic granulomatous disease (CGD), a deficiency in superoxide-producing neutrophils, suffer extreme microbial infections and often do not survive to adulthood (Segal, 1996). As there is no interference from an adaptive response, invertebrate models can be used to understand elements of the innate immune response to many pathogens.

There are obvious ethical concerns with using mammalian models for in vivo testing of microbial pathogens, many of which can be removed by employing invertebrate models. Invertebrates, such as insects, do not have a well-developed nervous system and consequently do not experience pain in the same manner as mammals. Although invertebrate models would not be the only source of in vivo testing, they have the potential to substantially reduce the number of mammals sacrificed. In addition using invertebrates as models to study the pathogenicity of microbes yields faster results.

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