The genetic architecture of immune defence in the nematode Caenorhabditis elegans

Nakad, Rania

To enhance fitness, any living organism should evaluate how much to invest in defence against pathogen threats. One likely advantageous strategy is pathogen avoidance behaviour. This defence response should be highly cost-effective, because it minimizes exposure to infection (and thus tissue damage), it minimizes spread of harmful pathogens, and it also minimizes self-damage caused by immunopathology upon activation of physiological immunity. Pathogen avoidance behaviour, as any other defence mechanism, is subject to strong selective pressure that results in specific variation in the underlying genes. Characterizing the genetics of these variations should provide information as to the type of genes and associated specific gene functions that are targeted by parasite-mediated selection. One of the tools employed to locate and identify the involved genes is Quantitative Trait Locus (QTL) analysis. For this PhD project, QTL analysis was used to characterize the genetic architecture of natural variation in C. elegans avoidance behaviour against the Gram-positive bacterium Bacillus thuringiensis. The analysis identified several genomic regions associated with variation in avoidance of pathogenic and/or non-pathogenic bacteria. Furthermore, our analysis showed significant epistatic interactions between some of the identified loci, suggesting a role of epistasis in determining behavioural defences. The main effect QTL for avoidance behaviour towards all tested bacteria encompasses the neuropeptide receptor gene npr-1, which has previously been shown to mediate behavioural defence against Pseudomonas aeruginosa. Interestingly, our results show that npr-1 is not the only gene mediating avoidance behaviour toward B. thuringiensis, and that different alleles of this gene have opposite effects on resistance (physiological and behavioural) in C. elegans. Moreover, our functional genetic analysis revealed that npr-1 influences survival and avoidance behaviour toward B. thuringiensis in the opposite direction than toward P. aeruginosa. Our findings thus suggest that npr-1 plays a central role in fine-tuning nematode behavioural defences to alternative stimuli. In addition, we evaluated whether C. elegans shows transgenerational immune priming of avoidance behaviour against B. thuringiensis. Interestingly, our results show that behavioural defences can be inherited from parents to offspring, with this response being dependent on the C. elegans isolate. This suggests that C. elegans can respond to pathogen challenge not only by individual activation of protective defences (e.g. avoidance behaviour) but also by transfer of such responses to the next generation. In parallel, we examined the role of one of the highly conserved signaling pathways, the insulin-like signaling cascade, in C. elegans’ defence. We specifically tested activation of the Foxo transcription factor DAF-16 by pathogenic strains of B. thuringiensis. Our results indicate that DAF-16 is directly activated by pathogens and that its activity is mainly determined by pathogenicity level and bacterial strain. Taken together, our observations from the different studies emphasize that C. elegans possesses a repertoire of alternative defence mechanisms that appear to be coordinated by a few central regulators (e.g., the neuropeptide receptor NPR-1 or the FOXO transcriptions factor DAF-16), that include physiological immune responses, avoidance behaviours and also transgenerational effects, and that also allows the nematode to differentiate between different pathogen taxa and additionally different strains of the same pathogen species.

Cite

Citation style:

Nakad, Rania: The genetic architecture of immune defence in the nematode Caenorhabditis elegans. 2013.

Rights

Use and reproduction:
No CC License (german copyright law applies)

Export