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.

免疫与营养是调控个体适合度的两大关键调节因子。然而，尽管免疫功能与营养对个体寿命及繁殖的影响已得到广泛证实，但取食行为、感染与免疫功能之间的相互作用仍未得到充分解析。探究生态与生理因素如何影响免疫应答及感染抗性，正是生态免疫学（eco-immunology）的核心研究主题。
本研究以黑腹果蝇（Drosophila melanogaster）为实验模型，探究经创伤感染后的宿主如何调节营养摄入，以及宏量营养素平衡如何影响宿主在感染革兰氏阳性致病菌藤黄微球菌（Micrococcus luteus）后的存活率。
研究结果显示，受感染的果蝇会维持碳水化合物摄入，但减少蛋白质摄入，相较于未感染组与假感染组果蝇，其蛋白与碳水化合物（P:C）摄入比从约1:4转变为约1:10。值得注意的是，当果蝇喂食低蛋白高碳水饮食时，藤黄微球菌感染后的果蝇死亡率显著降低，这表明果蝇通过调整宏量营养素摄入来实现针对细菌感染的营养性自我疗愈。
上述结果可能源于宏量营养素平衡对先天免疫基因组成型表达的调控作用：低蛋白高碳水饮食可显著上调关键抗菌肽（antimicrobial peptides）的表达水平。综上，本研究揭示了宏量营养素摄入与感染抗性之间的复杂关联，并将代谢与免疫通路间的分子互作整合至营养免疫学（nutritional immunology）的研究框架中。