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Updated: Jun 10, 2025
Using Eggs from Schistosoma mansoni as an In vivo Model of Helminth-induced Lung Inflammation
Published on: June 5, 2012
Liver Fibrosis Is Enhanced by a Higher Egg Burden in Younger Mice Infected with S. mansoni
Heike Müller1, Jan K Straßmann1, Anne S Baier1
1Department of Gastroenterology, Justus Liebig University, 35392 Giessen, Germany.
Abstract:
Schistosomiasis affects over 250 million people worldwide, with the highest prevalence at the age of 10-14 years. The influence of the host's age on the severity of liver damage is unclear. We infected male 8, 14, and 20-week-old mice with S. mansoni. Hepatic damage, inflammation, fibrosis, and metabolism were analyzed by RT-qPCR, Western blotting, ELISA, immunohistochemistry, and mechanistic transwell chamber experiments using S. mansoni eggs and human hepatic stellate cells (HSCs) or primary mouse hepatocytes. Major results were validated in human biopsies. We found that hepatosplenomegaly, granuloma size, egg load, inflammation, fibrosis, and glycogen stores all improved with the increasing age of the host. However, serum alanine transaminase (ALT) levels were lowest in young mice infected with S. mansoni. Hepatic carbohydrate exploitation was characterized by a shift towards Warburg-like glycolysis in S. mansoni-infected animals. Notably, S. mansoni eggs stimulated hepatic stellate cells to an alternatively activated phenotype (GFAP+/desmin+/αSMA-) that secretes IL-6 and MCP-1. The reduction of fibrosis in older age likely depends on the fine-tuning of regulatory and inflammatory cytokines, alternative HSC activation, and the age-dependent preservation of hepatic energy stores. The current results emphasize the significance of investigations on the clinical relevance of host age-dependent liver damage in patients with schistosomiasis.
Insights
Host age significantly impacts schistosomiasis liver damage severity. Older mice showed reduced inflammation and fibrosis, suggesting age-dependent protective mechanisms against schistosome infection.
Area of Science:
- * Parasitology and Immunology
- * Hepatology and Molecular Biology
Background:
- * Schistosomiasis infects over 250 million globally, with peak prevalence in adolescents (10-14 years).
- * The effect of host age on liver damage severity in schistosomiasis remains poorly understood.
Purpose of the Study:
- * To investigate the influence of host age on liver pathology and metabolic changes during Schistosoma mansoni infection.
- * To elucidate the mechanisms underlying age-dependent differences in hepatic damage and fibrosis.
Main Methods:
- * Infection of male mice (8, 14, 20 weeks old) with Schistosoma mansoni.
- * Analysis of hepatic damage, inflammation, and fibrosis using molecular and cellular assays (RT-qPCR, Western blotting, ELISA, immunohistochemistry).
- * In vitro studies with Schistosoma mansoni eggs, human hepatic stellate cells (HSCs), and primary mouse hepatocytes; validation in human liver biopsies.
Main Results:
- * Increasing host age correlated with reduced hepatosplenomegaly, granuloma size, inflammation, and fibrosis.
- * Younger infected mice exhibited the lowest serum alanine transaminase (ALT) levels, indicating distinct metabolic responses.
- * Schistosoma mansoni infection induced a Warburg-like glycolysis shift and alternatively activated HSCs (GFAP+/desmin+/αSMA-) secreting IL-6 and MCP-1.
Conclusions:
- * Host age modulates liver damage severity in schistosomiasis, with older hosts exhibiting improved outcomes.
- * Age-dependent fibrosis reduction is linked to cytokine regulation, alternative HSC activation, and preserved hepatic energy stores.
- * Further research into the clinical relevance of age-dependent liver damage in schistosomiasis patients is warranted.
