title: Activation of a G protein-coupled receptor by its endogenous ligand triggers the innate immune response of Caenorhabditis elegans.
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.
authors.affiliation: 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.
authors.forename: Olivier
authors.initials: O
authors.lastname: Zugasti
authors.affiliation: Department of Chemistry and Chemical Biology, Boyce Thompson Institute, Cornell University, Ithaca, New York, USA.
authors.forename: Neelanjan
authors.initials: N
authors.lastname: Bose
authors.affiliation: 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].
authors.forename: Barbara
authors.initials: B
authors.lastname: Squiban
authors.affiliation: 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.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Belougne
authors.affiliation: 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].
authors.forename: C Léopold
authors.initials: CL
authors.lastname: Kurz
authors.affiliation: Department of Chemistry and Chemical Biology, Boyce Thompson Institute, Cornell University, Ithaca, New York, USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Schroeder
authors.affiliation: 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.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pujol
authors.affiliation: 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.
authors.forename: Jonathan J
authors.identifier: 0000000212576862
authors.initials: JJ
authors.lastname: Ewbank
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000276:immunology*; D029742:Caenorhabditis elegans Proteins / Q000276:immunology*; D004817:Epidermis / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D008024:Ligands; D020935:MAP Kinase Signaling System / Q000276:immunology; D009181:Mycoses / Q000276:immunology*; D010666:Phenylpropionates / Q000276:immunology*; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000276:immunology*; D014947:Wounds and Injuries / Q000276:immunology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D008024:Ligands; D010666:Phenylpropionates; D043562:Receptors, G-Protein-Coupled; C569206:dihydrocaffeic acid receptor 1, C elegans; C001418:4-hydroxyphenyllactic acid
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