Macronutrients modulate survival to infection and immunity in Drosophila

Abstract

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 upregulation 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.

Viral susceptibility across host species is largely independent of dietary protein to carbohydrate ratios

“…Flies can respond to the absence of just one essential amino acid from their diet; increasing their appetite for foods rich in such amino acids (Kay et al, 2014; Keaton Wilson, Ruiz, & Davidowitz, 2019; Lochmiller & Deerenberg, 2000; McKean et al, 2008), suggesting they that they are constantly modifying their intake in response to internal cues. This mirrors the result of an experiment in rats, upon immune stimulation the rats actively ate more carbohydrates than fat, suggesting they wanted a direct source of energy and not just increased calories (Ponton et al, 2020). Whereas caterpillars infected with a nucleopolyhedrovirus, actively choose to feed on higher protein foods and as a result had stronger immune responses, including encapsulation, lysozyme-like antimicrobial activity and phenol-oxidase activity and decreased levels of infection (Leitao-Gonãlves et al, 2017).…”

Terminal investment strategies following infection are dependent on diet

“…Egg protein content may additionally be subject to trade‐offs against the immune response, evidenced by immune challenged female mosquitoes ( Anopheles gambiae ) laying eggs with lower protein content (Ahmed, Baggott, Maingon, & Hurd, ). Despite these findings, and a growing body of work showing an important role of dietary protein on immune responses (Lee, Cory, Wilson, Raubenheimer, & Simpson, ; Lee et al, ; Ponton et al, ), few studies have investigated how diet or specific nutrients influence terminal investment (Jacot et al, ; Krams et al, ).…”

Testing evolutionary explanations for the lifespan benefit of dietary restriction in fruit flies ( Drosophila melanogaster )

“…However, to date, none of these experiments have directly measured the key trait of lifetime survival. Additionally, studies often only use a small number of diets (Le Rohellec and Le Bourg 2009;Lee et al 2017;Kutzer et al 2018;Dinh et al 2019;Ponton et al 2020), or manipulate both P:C and calories at the same time (Le Rohellec and Le Bourg 2009; Lee et al 2017;Kutzer et al 2018), making it hard to disentangle that aspect of the diet is affecting survival with injury or infection. Furthermore, no experiments have directly compared the effect of multiple diets on lifetime survival and reproduction in control, injured, and infected individuals and thus tested the alternative predictions of the current evolutionary explanations of the DR response.…”