RRC ID 45908
Author Zugasti O, Bose N, Squiban B, Belougne J, Kurz CL, Schroeder FC, Pujol N, Ewbank JJ.
Title Activation of a G protein-coupled receptor by its endogenous ligand triggers the innate immune response of Caenorhabditis elegans.
Journal Nat Immunol
Abstract 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.
Volume 15(9)
Pages 833-8
Published 2014-9-1
DOI 10.1038/ni.2957
PII ni.2957
PMID 25086774
PMC PMC4139443
MeSH 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*
IF 20.479
Times Cited 48
WOS Category IMMUNOLOGY
Resource
C.elegans tm2484 tm3036 tm2487