Identification of a Conserved, Orphan G Protein-Coupled Receptor Required for Efficient Pathogen Clearance in Caenorhabditis elegans

ABSTRACT G protein-coupled receptors contribute to host defense across the animal kingdom, transducing many signals involved in both vertebrate and invertebrate immune responses. While it has become well established that the nematode worm Caenorhabditis elegans triggers innate immune responses following infection with numerous bacterial, fungal, and viral pathogens, the mechanisms by which C. elegans recognizes these pathogens have remained somewhat more elusive. C. elegans G protein-coupled receptors have been implicated in recognizing pathogen-associated damage and activating downstream host immune responses. Here we identify and characterize a novel G protein-coupled receptor required to regulate the C. elegans response to infection with Microbacterium nematophilum. We show that this receptor, which we designate pathogen clearance-defective receptor 1 (PCDR-1), is required for efficient pathogen clearance following infection. PCDR-1 acts upstream of multiple G proteins, including the C. elegans Gαq ortholog, EGL-30, in rectal epithelial cells to promote pathogen clearance via a novel mechanism.