Structural damage in the C. elegans epidermis causes release of STA-2 and induction of an innate immune response

Immunity. 2015 Feb 17;42(2):309-320. doi: 10.1016/j.immuni.2015.01.014.


The epidermis constantly encounters invasions that disrupt its architecture, yet whether the epidermal immune system utilizes damaged structures as danger signals to activate self-defense is unclear. Here, we used a C. elegans epidermis model in which skin-penetrating infection or injury activates immune defense and antimicrobial peptide (AMP) production. By systemically disrupting each architectural component, we found that only disturbance of the apical hemidesmosomes triggered an immune response and robust AMP expression. The epidermis recognized structural damage through hemidesmosomes associated with a STAT-like protein, whose disruption led to detachment of STA-2 molecules from hemidesmosomes and transcription of AMPs. This machinery enabled the epidermis to bypass certain signaling amplification and directly trigger AMP production when subjected to extensive architectural damage. Together, our findings uncover an evolutionarily conserved mechanism for the epithelial barriers to detect danger and activate immune defense.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / biosynthesis*
  • Antimicrobial Cationic Peptides / genetics
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans Proteins / immunology
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Adhesion Molecules / immunology
  • Cells, Cultured
  • Epidermis / immunology*
  • Epidermis / injuries*
  • Hemidesmosomes / immunology
  • Hemidesmosomes / pathology
  • Humans
  • Immunity, Innate
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • STAT Transcription Factors / metabolism*
  • Signal Transduction / immunology
  • p38 Mitogen-Activated Protein Kinases / immunology


  • Antimicrobial Cationic Peptides
  • Caenorhabditis elegans Proteins
  • Cell Adhesion Molecules
  • MUP-4 protein, C elegans
  • STA-2 protein, C elegans
  • STAT Transcription Factors
  • p38 Mitogen-Activated Protein Kinases