Nematode immunity

The importance of the innate immune system is underscored by its remarkable conservation in the immunity strategies of organisms from flies to mammals. In the July 26 Science, Kim et al. report the results of a genetic analysis of immune function in the nematode, Caenorhabditis elegans (Science 2002, 297:623-626). To screen for 'enhanced susceptibility to pathogen' (Esp) mutants, they monitored the response of mutagenized F2-generation larval-stage nematodes to infections with the bacterium Pseudomonas aeruginosa. Wild-type worms typically begin to die at around 34 hours. They screened 14,000 haploid genomes and identified several mutants that were killed by 31 hours. These strains were also hyper-sensitive to infection with Gram-positive pathogens. Kim et al. used high-resolution mapping of single-nucleotide polymorphisms (SNPs) to identify the mutant genes. Two of the Esp mutants had inactivating mutations in genes encoding components of the MAP kinase signal transduction pathway, namely sek-1 (an MKK3 homolog) and nsy-1 (an ASK1 homolog). Kim et al.then used RNAi experiments to demonstrate that the downstream transcription factor p38/pmk-1 is also required for pathogen defence.