Administration of β-glycolipids overcomes an unfavorable nutritional dependent host milieu: a role for a soy-free diet and natural ligands in intrahepatic CD8+ lymphocyte trapping and NKT cell redistribution

Soy-based diets are a major source of sphingolipids and play a complicated role in various aspects of the immune system. Administration of β-glycolipids, including β-glucosylceramide (GC), β-lactosylceramide (LC) and a 1:1 combination of GC and LC (IGL) were shown to exert immune-modulatory effects.AimTo examine the effects of a soy-free diet, and several β-glycolipids on concanavalin A (ConA)-induced hepatitis in the presence of an altered host glycolipid milieu.MethodsConA hepatitis was induced in C57BL/6 mice that were fed a soy-free diet (glycolipid content 200 μmol/kg). Two hours prior to administration of ConA, animals were injected IP with GC, LC, IGL or PBS. Animals were sacrificed 6 h after ConA administration.ResultsBoth a soy-free diet and administration of β-glycolipids were associated with significant alterations in the distribution of NKT cells. Specifically, there was a decrease in intrahepatic and an increase in intrasplenic NKT lymphocytes. β-glycolipids prevented the ConA-induced intrahepatic CD8 lymphocyte trapping, not seen in mice with only a soy-free diet. Both a soy-free diet and β-glycolipids alleviated ConA-induced hepatitis by inhibiting IL10 secretion and increasing IL12 serum levels. The effect of IGL was clinically and immunological superior to that of either glycolipid alone.ConclusionsBoth a soy-free diet and β-glycolipids can overcome the unfavorable host milieu in the setting of ConA hepatitis. The host glycolipid milieu profoundly influenced the immune and clinical effects of various insults, and suggests that alteration of the glycolipid background of the host can serve as a novel therapeutic tool.