It has long been known that C. elegans is attracted to nutritious bacteria but develops an avoidance response (termed aversion behaviour) to pathogens and toxins. However, the mechanisms underlying this discrimination remained elusive. In this study, Melo and Ruvkun assessed the effects of inactivating essential and metabolic genes in C. elegans using RNA interference (RNAi), including genes that encoded proteins involved in protein translation, the proteasome machinery and mitochondrial function. They found that disruption of the genes involved in essential cellular pathways triggered aversion behaviour to Escherichia coli, which is a normal (attractive) food source for C. elegans. Similarly, disruption of these core cellular components by chemical toxins resulted in aversion behaviour, which suggests that, in C. elegans, the disturbance of basic cellular processes by toxins is sensed by a surveillance system that also senses pathogens.
Next, the investigators analysed the transcriptional expression of immune genes in response to the disruption of central cellular activities. RNAi-mediated inactivation of essential genes triggered innate immune transcriptional programmes in the absence of pathogens or toxins. The xenobiotic detoxification response was also induced, suggesting that the surveillance pathway in C. elegans simultaneously triggers pathways that mediate pathogen clearance and xenobiotic detoxification. Furthermore, the authors found that the aversion behaviour depended on components of the JUN N-terminal kinase-like pathway and on serotonin biosynthesis. The requirement for serotonin suggests a dependence on a neuroendocrine circuit.
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