The fatty acid oleate is required for innate immune activation and pathogen defense in Caenorhabditis elegans

Fatty acids affect a number of physiological processes, in addition to forming the building blocks of membranes and body fat stores. In this study, we uncover a role for the monounsaturated fatty acid oleate in the innate immune response of the nematode Caenorhabditis elegans. From an RNAi screen for regulators of innate immune defense genes, we identified the two stearoyl-coenzyme A desaturases that synthesize oleate in C. elegans. We show that the synthesis of oleate is necessary for the pathogen-mediated induction of immune defense genes. Accordingly, C. elegans deficient in oleate production are hypersusceptible to infection with diverse human pathogens, which can be rescued by the addition of exogenous oleate. However, oleate is not sufficient to drive protective immune activation. Together, these data add to the known health-promoting effects of monounsaturated fatty acids, and suggest an ancient link between nutrient stores, metabolism, and host susceptibility to bacterial infection. Author summary The evolution of multicellular organisms has been shaped by their interactions with pathogenic microorganisms. The microscopic nematode C. elegans eats bacteria for food and has evolved inducible immune defenses toward ingested pathogens that are coordinated within intestinal epithelial cells. C. elegans, therefore, presents a genetic system to characterize the requirements for the activation of innate immune defenses. Here, we show that the monounsaturated fatty acid oleate is necessary for the induction of innate immune defenses and for protection against bacterial pathogens, which defines a new link between metabolism and the regulation of anti-pathogen responses in a metazoan host.