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 |