Hormesis results in trade-offs with immunity

Abstract

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, artifacts 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 that lack key components of antifungal 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 artifacts 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."

Keywords: Drosophila melanogaster; ecological immunity; fitness; hormesis; life-history evolution; trade-offs.

Figure 1

Percentage of flies surviving 20 h post heat stress following topical exposure to heat-killed fungal pathogens at different dose regimes (±SE).

Figure 2

(A) Mean longevity of each genotype. Black indicates flies treated with a sham treatment (control) and gray indicates pathogen-challenged flies (±SE). Average life spans were not used in the original analysis as mortality patterns did not meet the assumptions of ANOVA investigation. (B) The influence of the topical exposure to a heat-killed fungal pathogen on the relative hazard ratio parameters to untreated flies (dashed line). Cox hazard proportions are shown for knockdown (KD) and knockout (KO) mutants in gray, and their associated pooled control genotypes (Con) in black (±SE). Values under the dashed line indicate that pathogen-challenged animals have increased survival; values above indicate that pathogen-challenged animals experience reduced survival.

Figure 3

Evidence that pathogen-challenged flies experience increased survival, increased fecundity but increased susceptibility to infection in outbred lines. Estimated %change in trait values are reported ±SE. Dahomey line is indicated in black; Oregon-R line is indicated in gray.