Caenorhabditis elegans beta-catenin and a downstream homeobox transcription factor are required for defense against pathogenic attack.
Javier E. Irazoqui and Frederick M. Ausubel
The soil-dwelling nematode Caenorhabditis elegans is susceptible to pathogenic attack by bacteria, such as the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. Using this model system for host-pathogen interactions, we have uncovered a requirement for the β-catenin homolog BAR-1 in defense against pathogens. Compared to wild type, bar-1 mutant animals are much more sensitive to both human pathogens. RNA-mediated inhibition of the BAR-1 negative regulator GSK-3, or mutation of the axin homolog PRY-1, increased the resistance to S. aureus, suggesting that the levels of BAR-1 are important for defense. Of three downstream homeobox-containing BAR-1 target genes, only mutation of EGL-5 caused sensitivity both to S. aureus and P. aeruginosa. Basal expression and induction of a GFP-based reporter construct, which is induced upon exposure to S. aureus, are reduced in vivo by RNAi of BAR-1. BAR-1 RNAi also suppresses the enhanced resistance exhibited by daf-2 loss of function mutants, suggesting that BAR-1 acts downstream or in parallel to DAF-2. These data suggest that BAR-1/β-catenin has a novel role in innate immune defense, mediated by the transcription factor EGL-5, and parallel to the DAF-2/insulin signaling pathway.