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Immunogenetics

C. elegans — an innate choice?

Nature Reviews Genetics volume 3, page 651 (2002)Cite this article

Kim et al. assayed the progeny of mutagenized worms, which had been exposed to the bacterium Pseu-domonas aeruginosa for enhanced susceptibility to pathogen (esp) infection. From a screen of 14,000 haploid genomes, they isolated two mutants, esp2 and esp8, that die much faster on exposure to P. aeruginosa than wild-type worms do. High-resolution SNP mapping revealed the chromosomal locations of the mutant genes, which were identified by phenotypic rescue — the esp2 mutant was rescued by the gene sek-1 , and esp8 by nsy-1 .

sek-1 encodes a MAP kinase kinase (MAPKK) homologue of mammalian MKK3/MKK6 and MKK4, and nsy-1 encodes an orthologue of the mammalian MAPKKK ASK1. Because these kinases activate the p38 kinase family and the JNK MAP kinases in mammals, the authors tested the role of p38 and JNK in the C. elegans defence response. The esp2 and esp8 mutants had markedly reduced levels of p38 MAPK activity. Moreover, the knockdown of pmk-1 , one of two C. elegans p38 orthologues, by RNA interference produced a strong esp phenotype. Knockdown of pmk-2 and a jnk mutation, however, produced no enhanced susceptiblity to P. aeruginosa infection. Together these results show that the p38 MAPK pathway is required for innate responses to pathogen infection, which is an important discovery as this signalling pathway is also crucially required in mammals for inflammatory and innate-immune response signalling pathways.

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References

ORIGINAL RESEARCH PAPERS

  1. Kim, D. H. et al. A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297, 623–626 (2002)

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  2. Mallo, G. V. et al. Inducible antibacterial defense system in C. elegans. Curr. Biol. 12, 1209–1214 (2002)

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FURTHER READING

  1. Kimbrell, D. & Beutler, B. The evolution and genetics of innate immunity. Nature Rev. Genet. 2, 256–267 (2001)

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Authors
  1. Jane Alfred
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Alfred, J. C. elegans — an innate choice?. Nat Rev Genet 3, 651 (2002). https://doi.org/10.1038/nrg893

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