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

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

Author information

1
1] Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Case 906, Marseille, France. [2] INSERM, U1104, 13288 Marseille, France. [3] CNRS, UMR7280, Marseille, France.
2
Department of Chemistry and Chemical Biology, Boyce Thompson Institute, Cornell University, Ithaca, New York, USA.
3
1] Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Case 906, Marseille, France. [2] INSERM, U1104, 13288 Marseille, France. [3] CNRS, UMR7280, Marseille, France. [4].

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.

PMID:
25086774
PMCID:
PMC4139443
DOI:
10.1038/ni.2957
[Indexed for MEDLINE]
Free PMC Article

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