GPA-9 is a novel regulator of innate immunity against Escherichia coli foods in adult Caenorhabditis elegans.

Innate immune responses to pathogens are governed by the nervous system. Here, we investigated the molecular mechanism underlying innate immunity in Caenorhabditis elegans against Escherichia coli OP50, a standard laboratory C. elegans food. Longevity was compared in worms fed live or UV-killed OP50 at low or high density food condition (HDF). Expression of the antimicrobial gene lys-8 was approximately 5-fold higher in worms fed live OP50, suggesting activation of innate immunity upon recognition of OP50 metabolites. Lifespan was extended and SOD-3 mRNA levels were increased in gpa-9-overexpressing gpa-9XS worms under HDF in association with robust induction of insulin/IGF-1 signaling (IIS). Expression of ins-7 and daf-28 that control lys-8 expression was reduced in gpa-9XS, indicating that GPA-9-mediated immunity is due in part to ins-7 and daf-28 downregulation. Our results suggest that OP50 metabolites in amphid neurons elicit innate immunity through the IIS pathway, and identify GPA-9 as a novel regulator of both the immune system and aging in C. elegans.