Genetic dissection of innate immune memory in Drosophila melanogaster

Current studies have demonstrated that innate immunity possesses memory characteristics. Although the molecular mechanisms underlying innate immune memory have been addressed by numerous studies, genetic variations in innate immune memory and the associated genes remain unclear. Here, we explored innate immune memory in 163 lines of Drosophila melanogaster from the Drosophila Synthetic Population Resource. In our assay system, prior training with low pathogenic bacteria (Micrococcus luteus) increased the survival rate of flies after subsequent challenge with highly pathogenic bacteria (Staphylococcus aureus). This positive training effect was observed in most lines, but some lines exhibited negative training effects. Survival rates under training and control conditions were poorly correlated, suggesting that distinct genetic factors regulate training effects and normal immune responses. Subsequent quantitative trait loci analysis suggested that four loci containing 80 genes may be involved in regulating innate immune memory. Among them, Adgf-A, which encodes an extracellular adenosine deaminase-related growth factor, was shown to be associated with training effects. Our study findings help to elucidate the genetic architecture of innate immune memory in Drosophila and may provide insight for new therapeutic treatments aimed at boosting immunity.