Adaptation Against Long-Term Protein Deprivation Trades Off With Immunocompetence And The Ability To Survive Pathogenic Infections

Insufficient protein intake, leading to malnutrition, is a major global health concern that compromises the immune system and increases susceptibility to diseases. In scenarios where protein availability is constrained, organisms may experience strong selection to efficiently allocate their resources between immunity vs other energy-demanding processes, such as reproduction, resulting in evolutionary trade-offs. Additionally, in many species, protein deficiency has a more significant impact on female reproduction than on males, potentially leading to pronounced sexually dimorphic trade-offs involving immunity and infection outcomes. However, there are no experiments to test these possibilities. In this work, we demonstrate that in Drosophila melanogaster populations selected for increased early-life reproduction under protein limitations, evolved virgin females indeed suffered a greater reduction in their resistance to the pathogen Providencia rettgeri and showed lower survival following infection than males, corroborating our expectations. However, mating resulted in a loss of sexually dimorphic infection outcomes, causing both sexes to exhibit nearly identical infection costs and reduced infection tolerance compared to their ancestral, unselected populations. Moreover, several immune components, including the Toll- and IMD-mediated inducible immune pathways, were either less upregulated or more downregulated in the selected flies, which may contribute to their heightened susceptibility to pathogens. Downregulation in key metabolic pathways and genes related to phagocytosis, melanisation and ROS-mediated defence after infection in selected flies can also be associated with their increased pathogen vulnerability. Taken together, our work thus reveals the reproductive status- and sex-specific plasticity of immune investments and post-infection health in response to evolutionary constraints under chronic protein deprivation.