Adaptation to a Lower Protein Diet Before Reproduction Trades off with Immunocompetence and the Ability to Survive Pathogenic Infections

Insufficient protein intake causes malnutrition, compromising immunity and increasing the risk of pathogenic infections. In fact, under limited protein availability, organisms may experience stronger selective pressure to optimally allocate their resources between immunity vs other energy-demanding processes, such as reproduction, resulting in evolutionary trade-offs. In many species, protein deficiency may also more strongly affect female reproduction, leading to sexually-dimorphic trade-offs involving immunity and infection outcomes, though these haven't been experimentally tested. Here, we demonstrate that in Drosophila melanogaster populations evolving greater investment in early-reproduction in response to a lower-protein diet before oviposition, unmated females exhibited lower post-infection survival against Providencia rettgeri than unmated males, corroborating our prediction. However, mating eliminated these sex differences, with both sexes exhibiting nearly identical infection costs and reduced post-infection survival compared with their unselected counterparts. Overall, selected flies also had lower infection tolerance, although the effect on pathogen resistance was weak and inconsistent. Immune responses, including Toll- and IMD-mediated pathways, were either less upregulated or more downregulated in selected flies, which could explain their increased pathogen susceptibility. Downregulated metabolic pathways may also play a role. Overall, this study offers new evolutionary insights into how low-protein diets drive sex- and reproductive-status-specific variations in immunity and health.