Activation of a G protein-coupled receptor by its endogenous ligand triggers the innate immune response of Caenorhabditis elegans

Nat Immunol. 2014 Sep;15(9):833-8. doi: 10.1038/ni.2957. Epub 2014 Aug 3.


Immune defenses are triggered by microbe-associated molecular patterns or as a result of damage to host cells. The elicitors of immune responses in the nematode Caenorhabditis elegans are unclear. Using a genome-wide RNA-mediated interference (RNAi) screen, we identified the G protein-coupled receptor (GPCR) DCAR-1 as being required for the response to fungal infection and wounding. DCAR-1 acted in the epidermis to regulate the expression of antimicrobial peptides via a conserved p38 mitogen-activated protein kinase pathway. Through targeted metabolomics analysis we identified the tyrosine derivative 4-hydroxyphenyllactic acid (HPLA) as an endogenous ligand. Our findings reveal DCAR-1 and its cognate ligand HPLA to be triggers of the epidermal innate immune response in C. elegans and highlight the ancient role of GPCRs in host defense.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans Proteins / immunology*
  • Epidermis / immunology*
  • Immunity, Innate / immunology*
  • Ligands
  • MAP Kinase Signaling System / immunology
  • Mycoses / immunology*
  • Phenylpropionates / immunology*
  • RNA Interference
  • Receptors, G-Protein-Coupled / immunology*
  • Wounds and Injuries / immunology*


  • Caenorhabditis elegans Proteins
  • Ligands
  • Phenylpropionates
  • Receptors, G-Protein-Coupled
  • dihydrocaffeic acid receptor 1, C elegans
  • 4-hydroxyphenyllactic acid