Hormesis results in trade-offs with immunity

Many have argued that we may be able to extend life and improve human health through hormesis, the beneficial effects of low-level toxins and other stressors. But, studies of hormesis in model systems have not yet established whether stress-induced benefits are cost-free, artefacts of inbreeding, or come with deleterious side-effects. Here we provide evidence that hormesis results in trade-offs with immunity. We find that a single topical dose of dead spores of the entomopathogenic fungus, Metarhizium robertsii, increases the longevity of the fruit fly, Drosophila melanogaster, without significant decreases in fecundity. We find that hormetic benefits of pathogen challenge are greater in lines which lack key components of anti-fungal immunity (Dif and Turandot M). And, in outbred fly lines, we find that topical pathogen challenge enhances both survival and fecundity, but reduces ability to fight off live infections. The results provide evidence that hormesis is manifested by stress-induced trade-offs with immunity, not cost-free benefits or artefacts of inbreeding. Our findings illuminate mechanisms underlying pathogen-induced life history trade-offs, and indicate that reduced immune function may be an ironic side-effect of the “elixirs of life.”