The role of C-type lectin-like domain genes in C. elegans immunity

C-type lectin-like domain (CTLD) proteins are mainly known for their crucial roles in vertebrate immunity acting either as pattern recognition receptors or antimicrobial peptides. In invertebrates the exact immune function of CTLD proteins is less described despite of the abundance of their encoding genes in many metazoan genomes. Caenorhabditis elegans particularly stands out for its enormous set of diversified CTLD proteins. Surprisingly, their exact contribution to C. elegans immunity still remains elusive. During my PhD I systematically screened the CTLD gene (clec) repertoire of C. elegans to identify genes that are involved in the defense against the two pathogens Pseudomonas aeruginosa and Bacillus thuringiensis (BT). Unexpectedly, in the tested mutants clec-knock-out led equally to susceptibility and resistance to infection, indicating that clec genes mediate both immune activation and suppression. Resistance of clec mutants on BT could partially be explained by enhanced pathogen avoidance behavior. We could confirm for the clec gene C54G4.4 that it negatively regulates behavioral immune responses and thus demonstrated that beside a potential contribution to the physiological, clec genes might also function in behavioral immunity. In parallel we analyzed the expression of clec genes upon infection and stress. We identified clec-4 as another interesting candidate due to its highly up-regulated profile upon exposure to many pathogens and stresses. Surprisingly, the clec-4 mutant showed resistance towards BT infection, suggesting a function in negative regulation of the immune response. We further examined the role of a co-expressed clec-4 paralog, clec-41, which was required for defense against BT and suppressed the resistance phenotype of the clec 4 mutant. These findings give hint to a complex regulation network of interacting clec genes. Taken together, our work is the first step towards a more detailed analysis of the exact clec function in immunity.


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