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.
