Schistosoma mansoni egg-derived antigens stimulate metabolic activity in the liver and colon by engaging insulin-like growth factor-1 receptor signaling pathways

Background: Schistosomiasis, a parasitic disease affecting over 250 million people, is mainly driven by tissue damage caused by schistosome eggs rather than adult worms. The mechanism by which egg antigens transmit signals into host cells is unclear. This study explores whether S. mansoni egg antigens regulate the metabolic activity of hepatocytes and enterocytes via the insulin/IGF-1 receptor pathway.

Methods: Eight-week-old mice were infected with S. mansoni cercariae using the paddling technique. We employed RT-PCR array, western blotting, and immunohistochemistry to analyze markers of insulin/IGF-1 receptor signaling in liver and colon. We performed functional experiments on colon epithelial cell lines, including western blotting and AP-1 promoter activity assessment.

Results: S. mansoni infection significantly upregulated genes like Igf2, Dok, Aebp1, Leptin, and Akt3, with Serpine1 being the most induced, while downregulating Sos1, Irs1, and Gck, with G6pc most reduced. The insulin/IGF-1 receptor was notably activated in human perigranulomatous hepatocytes. Using the inhibitor BMS 536924, mechanistic experiments showed that S. mansoni egg antigens activated the insulin/IGF-1 receptor signaling cascade, including c-Jun activation.

Conclusions: In conclusion, our findings demonstrate that S. mansoni soluble egg antigens modulate the insulin/IGF-1 receptor signaling pathway in both murine and human hepatocytes and enterocytes, leading to an inhibition of gluconeogenesis. Thus, the parasite's soluble egg antigens may enhance insulin sensitivity in the host. However, the concurrent activation of the proto-oncogene c-Jun through this signaling pathway raises the possibility of potential morbidity associated with this mechanism.

Publication History

Article published online:
20 January 2025