A high-sugar diet affects cellular and humoral immune responses in Drosophila.

A high-sugar diet (HSD) induces Type 2 diabetes (T2D) and obesity, which severely threaten human health. The Drosophila T2D model has been constructed to study the mechanisms of insulin resistance, diet-induced cardiovascular diseases and other conditions. Innate immunity is the first line of defense against invading pathogens and parasites. However, few studies have focused on the relationship between a HSD and the innate immune response in Drosophila. In this study, we fed flies a high-sucrose diet and observed defects in the phagocytosis of latex beads and B. bassiana spores. The actin cytoskeleton was also disrupted in hemocytes from HSD-fed larvae. Furthermore, HSD induced the differentiation of lamellocytes in the lymph gland and circulating hemolymph, which rarely occurs in healthy bodies, via JNK signaling. In addition, the Toll and JNK pathways were excessively activated in the fat bodies of HSD-fed larvae, and a large number of dead cells were observed. Finally, HSD induced the aberrant activation of the innate immune system, including inflammation. Our results have established a connection between T2D and the innate immune response.