Conditioning Protects C. elegans from Lethal Effects of Enteropathogenic E. coli by Activating Genes that Regulate Lifespan and Innate Immunity

Abstract

Caenorhabditis elegans exhibits avoidance behavior when presented with diverse bacterial pathogens. We hypothesized that exposure to pathogens might not only cause worms to move away but also simulta- neously activate pathways that promote resistance to the pathogen. We show that brief exposure to virulent or avirulent strains of the bacterial pathogen entero- pathogenic E. coli (EPEC) ‘‘immunizes’’ C. elegans to survive a subsequent exposure that would other- wise prove lethal, a phenomenon we refer to as ‘‘conditioning.’’ Conditioning requires dopaminergic neurons; the p38 MAP kinase pathway, which regu- lates innate immunity; and the insulin/IGFR pathway, which regulates lifespan. Our findings suggest that the molecular pathways that control innate immunity and lifespan may be regulated or ‘‘conditioned’’ by exposure to pathogens to allow survival in noxious environments.