Department of Entomology, Cornell University, Ithaca, New York, United States of America.
PLoS Genet. 2015 Mar 12;11(3):e1005030. doi: 10.1371/journal.pgen.1005030. eCollection 2015 Mar.
Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and "nutritional immunology" has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional "immune system" that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment.
营养不良和营养不足都可能导致多种动物的免疫防御受损，因此“营养免疫学”被认为是理解免疫和确定抗感染策略的一种手段。然而，饮食对免疫的影响的遗传基础在很大程度上是未知的。在本研究中，我们在黑腹果蝇中进行了全基因组关联作图，以确定个体对抵抗力的遗传基础，以及对饮食的免疫敏感性的变化（基因型与环境的相互作用，或 GxE）。黑腹果蝇在高葡萄糖或低葡萄糖饮食中被饲养几代，然后用普罗维登斯雷氏菌（一种黑腹果蝇的天然细菌病原体）感染。在感染强度高峰时测量系统病原体负荷，并从每种饮食饲养的未感染果蝇中获取几个营养状况指标。我们发现，饮食中的葡萄糖水平显著改变了免疫防御的质量，高葡萄糖饮食导致更高的病原体负荷。在抽样人群中，免疫防御的质量在遗传上是可变的，我们发现对饮食葡萄糖的免疫敏感性存在遗传变异（基因型与饮食的相互作用）。在高葡萄糖饮食中饲养的果蝇中，免疫防御与代谢状态的指标在遗传上相关，我们鉴定出多个解释免疫防御变异的基因，包括一些以前未涉及免疫反应但经 RNAi 敲低后证实能改变病原体负荷的基因。我们的发现强调了饮食成分对免疫防御的重要性，并揭示了传统“免疫系统”之外的基因在决定对感染的易感性方面可能很重要。这些基因的功能变异在自然种群中是分离的，为在营养环境背景下对病原体压力的进化反应提供了基础。
