A role for SKN-1/Nrf in pathogen resistance and immunosenescence in Caenorhabditis elegans

PLoS Pathog. 2012;8(4):e1002673. doi: 10.1371/journal.ppat.1002673. Epub 2012 Apr 26.


A proper immune response ensures survival in a hostile environment and promotes longevity. Recent evidence indicates that innate immunity, beyond antimicrobial effectors, also relies on host-defensive mechanisms. The Caenorhabditis elegans transcription factor SKN-1 regulates xenobiotic and oxidative stress responses and contributes to longevity, however, its role in immune defense is unknown. Here we show that SKN-1 is required for C. elegans pathogen resistance against both Gram-negative Pseudomonas aeruginosa and Gram-positive Enterococcus faecalis bacteria. Exposure to P. aeruginosa leads to SKN-1 accumulation in intestinal nuclei and transcriptional activation of two SKN-1 target genes, gcs-1 and gst-4. Both the Toll/IL-1 Receptor domain protein TIR-1 and the p38 MAPK PMK-1 are required for SKN-1 activation by PA14 exposure. We demonstrate an early onset of immunosenescence with a concomitant age-dependent decline in SKN-1-dependent target gene activation, and a requirement of SKN-1 to enhance pathogen resistance in response to longevity-promoting interventions, such as reduced insulin/IGF-like signaling and preconditioning H(2)O(2) treatment. Finally, we find that wdr-23(RNAi)-mediated constitutive SKN-1 activation results in excessive transcription of target genes, confers oxidative stress tolerance, but impairs pathogen resistance. Our findings identify SKN-1 as a novel regulator of innate immunity, suggests its involvement in immunosenescence and provide an important crosstalk between pathogenic stress signaling and the xenobiotic/oxidative stress response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / immunology*
  • DNA-Binding Proteins / immunology*
  • Enterococcus faecalis / immunology
  • Gene Expression Regulation
  • Immunity, Innate
  • Oxidative Stress
  • Pseudomonas aeruginosa / immunology
  • RNA Interference
  • Signal Transduction
  • Transcription Factors / immunology*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Transcription Factors
  • skn-1 protein, C elegans
  • p38 Mitogen-Activated Protein Kinases