The Emerging Role of 3-Hydroxyanthranilic Acid onC. elegansAging Immune Function

Abstract

Abstract3-hydroxyanthranilic acid (3HAA) is considered to be a fleeting metabolic intermediate along tryptophan catabolism through the kynurenine pathway. 3HAA and the rest of the kynurenine pathway have been linked to immune response in mammals yet whether it is detrimental or advantageous is a point of contention. Recently we have shown that accumulation of this metabolite, either through supplementation or prevention of its degradation, extends healthy lifespan inC. elegansand mice, while the mechanism remained unknown. UtilizingC. elegansas a model we investigate how 3HAA andhaao-1inhibition impact the host and the potential pathogens. What we find is that 3HAA improves host immune function with aging and serves as an antimicrobial against gram-negative bacteria. Regulation of 3HAA’s antimicrobial activity is accomplished via tissue separation. 3HAA is synthesized in theC. eleganshypodermal tissue, localized to the site of pathogen interaction within the gut granules, and degraded in the neuronal cells. This tissue separation creates a new possible function for 3HAA that may give insight to a larger evolutionarily conserved function within the immune response.Graphical Abstract