Caenorhabditis elegans: an emerging genetic model for the study of innate immunity

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Abstract
Interest in innate immunity, the first line of defence of multicellular organisms against infection, has been reawakened in recent years. The mechanisms that are involved are evolutionarily ancient, as shown by the remarkable conservation of the Toll signalling pathway between the model insect Drosophila melanogaster and mammals. The nematode Caenorhabditis elegans has proved its worth as a model organism in fields such as apoptosis and nervous-system development, partly because it possesses many advantages for genetic studies (for example, rapid life cycle, self-fertilization, a large number of progeny and a large mutant collection). This microscopic worm normally lives in the soil where it is in permanent competition with potentially pathogenic bacteria and fungi. But, even after its genome was sequenced, comparisons with Drosophila and other animals raised the question of whether it possesses inducible defence mechanisms against microorganisms. Recently, two signalling pathways that are necessary for the resistance of worms to bacterial infection were identified — the MAPK and TGF-β pathways. Using these signalling cascades, the nematode can integrate infection-associated inputs and respond with specific effectors that contribute to better resistance. However, these pathways are also used in other contexts — for example, during development, which indicates a complex regulation of the relevant signalling cascades. Despite the fact that the similarities with the known components of insect or mammalian immunity are weak, the general defence strategy (recognition, signalling, response) is conserved. So the nematode has the potential to teach us much about the evolutionary origins of immunity, and might reveal as yet uncharacterized aspects of mammalian defences against infection. Importantly, a two-sided approach can be taken with C. elegans, as it can be used to investigate the virulence mechanisms of pathogens. So, with worms, the equilibrium between host and pathogen can be readily addressed.