Innate immune responses to pathogens are governed by the nervous system. Here, we investigated the mechanism underlying innate immunity in the nematode C. elegans against E. coli OP50, a standard laboratory C. elegans food. Longevity was compared in worms fed live or UV-killed OP50 at low or high density. 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 high density food conditions in association with robust induction of insulin/IGF 1 signaling. Expression of
daf-28, an insulin-like peptide that controls
lys-8 expression, was reduced in the gpa-9XS strain, indicating that GPA-9-mediated immunity is due in part to
daf-28 down regulation. Collectively, our results suggest that OP50 metabolites in ASJ neurons elicit innate immunity in C. elegans through the insulin/IGF-1 signaling pathway, and identify GPA-9 as a novel regulator of both the immune system and aging in C. elegans. (This study was supported by a grant from the Korean Health 21 R&D Project, Ministry of Health, Welfare and Family Affairs, Republic of Korea, [A030003] and Korean Research WCU grant R31-2008-000-10086-0).