Parasite eggs induce metabolic stress in Schistosoma mansoni-infected hamster livers

Question Schistosomiasis is one of the most common parasitic diseases, affecting approximately 240 million people worldwide. During egg deposition, many of the parasite eggs are swept away in the host circulation via the mesenteric vessels and become trapped in the liver. Subsequently, granuloma formation and a fibrotic-inflammatory remodelling are induced. Results of previous studies demonstrated that an infection with Schistosoma mansoni influences the hepatic carbohydrate metabolism. The aim of the present study was the characterization and mechanistic analysis of the alterations in the hepatic carbohydrate metabolism induced by secreted factors of S. mansoni eggs.

Methods The expression of key enzymes of the hepatic carbohydrate metabolism was analyzed by western blot and immunohistochemistry in liver lysates of S. mansoni bisex-infected hamsters (n = 5, age 4.5 months, 7 weeks after infection). Singlesex-infected hamsters (n = 5) and non-infected hamsters (n = 3) served as controls. The hepatic glycogen content was measured by a quantitative assay. In addition, enzymatic and signaling pathway-associated relationships were mechanistically demonstrated by stimulation and inhibition experiments.

Results In comparison to non-infected and singlesex-infected control animals, the key enzymes of glycolysis were induced in S. mansoni bisex infected hamster livers, while gluconeogenesis was not affected. In addition, the key enzymes of glycogen metabolism as well as hepatic glycogen were decreased to 20 % of the normal value of healthy controls. In contrast, glycogen content appeared enriched in the parasitic eggs, whereas an exhaustive depletion of glycogen in the parenchyma was demonstrated by periodic acid‐Schiff (PAS)-staining. The results from the hamster model were supported by data of in vitro experiments, which aimed at stimulating HepG2 cells with soluble egg antigen (SEA) and inhibiting central metabolic signaling pathways (Akt, AMPK).

Conclusions The increased hepatic energy supply is probably important for the maintenance of the vital functions of the eggs, including embryogenesis. These results of the hamster model might explain the extended survival (months) of hepatic eggs from S. mansoni in comparison to the short survival period after excretion (days). In addition, the parasite appears to control these processes actively as secreted factors of the eggs activate the relevant metabolic pathways in cell culture.

Publication History

Article published online:
04 January 2021