Mounting an immune response is incredibly energetically demanding. Activation of the immune system requires mobilization of cellular energy, and sustained infection drains metabolic stores. Regulation of the immune response is therefore mechanistically linked to metabolic regulation, and dietary nutrition can have an enormous impact on capacity for immune defense. Our research team and others have shown that D. melanogaster and other insects become more susceptible to infection when they are provided with high-sugar diets. Conversely, diets that are high in protein can promote immunity. Remarkably, however, individuals in natural populations of D. melanogaster show genetic diversity in their immunological sensitivity to diet. This “genotype-by-environment interaction” means that some individuals are genetically predisposed to suffer much greater reductions in immune defense when provided with high-sugar diets.

Crucially, the host is itself the environment in which the infecting pathogen lives. D. melanogaster provided with high-sugar diets become hyperglycemic and hyperlipidemic. This extra sugar and fat inside the host body may be acquired by the pathogen, promoting pathogen proliferation and increasing infection severity. This can happen independently of any direct effects of metabolic state on immune system function. The distinct effects of metabolic state on host immune function and pathogen growth potential could synergize to dramatically alter host sensitivity to infection, depending on the pathogen capacity to access host nutrients and the host immunological response to increased pathogen proliferation.

In ongoing research, we are testing mechanisms by which diet can influence the quality of the immune response and we are evaluating the responsiveness of various bacterial pathogens to host metabolic state. Because metabolic regulation and bacterial infection mechanisms are very highly conserved across all animals, our conclusions from the D. melanogaster experimental system are likely to have broad relevance to bacterial infections of other animals including humans.