Macronutrients modulate survival to infection and immunity in Drosophila

Immunity and nutrition are two essential modulators of individual fitness.
However, while the implications of immune function and nutrition on an
individual’s lifespan and reproduction are well established, the interplay
between feeding behaviour, infection, and immune function, remains poorly
understood. Asking how ecological and physiological factors affect immune
responses and resistance to infections is a central theme of
eco-immunology. In this study, we used the fruit fly, Drosophila
melanogaster, to investigate how infection through septic injury modulates
nutritional intake, and how macronutrient balance affects survival to
infection by the pathogenic Gram-positive bacterium Micrococcus luteus.
Our results show that infected flies maintain carbohydrate intake, but
reduce protein intake, thereby shifting from a protein-to-carbohydrate
(P:C) ratio of ~1:4 to ~1:10 relative to non-infected and sham-infected
flies. Strikingly, the proportion of flies dying after M. luteus infection
was significantly lower when flies were fed a low-P high-C diet, revealing
that flies shift their macronutrient intake as means of nutritional
self-medication against bacterial infection. These results are likely due
to the effects of the macronutrient balance on the regulation of the
constitutive expression of innate immune genes, as a low-P high-C diet was
linked to an up-regulation in the expression of key antimicrobial
peptides. Together, our results reveal the intricate relationship between
macronutrient intake and resistance to infection, and integrate the
molecular cross-talk between metabolic and immune pathways into the
framework of nutritional immunology.