| Autor: |
Müller H; Department of Gastroenterology, Justus Liebig University, 35392 Giessen, Germany., Straßmann JK; Department of Gastroenterology, Justus Liebig University, 35392 Giessen, Germany., Baier AS; Department of Gastroenterology, Justus Liebig University, 35392 Giessen, Germany., von Bülow V; Department of Gastroenterology, Justus Liebig University, 35392 Giessen, Germany., Stettler F; Department of Gastroenterology, Justus Liebig University, 35392 Giessen, Germany., Hagen MJ; Department of Gastroenterology, Justus Liebig University, 35392 Giessen, Germany., Schmidt FP; Department of Gastroenterology, Justus Liebig University, 35392 Giessen, Germany., Tschuschner A; Department of Gastroenterology, Justus Liebig University, 35392 Giessen, Germany., Schmid AR; Department of Internal Medicine III, Justus Liebig University, 35392 Giessen, Germany., Zahner D; Central Laboratory Animal Facility, Justus Liebig University, 35392 Giessen, Germany., Köhler K; Institute of Veterinary Pathology, Justus Liebig University, 35392, Germany., Pons-Kühnemann J; Institute of Medical Informatics, Justus Liebig University, 35392, Germany., Leufkens D; Institute of Medical Informatics, Justus Liebig University, 35392, Germany., Glebe D; Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, German Center for Infection Research (DZIF; Partner Site Giessen-Marburg-Langen), Justus Liebig University, 35392 Giessen, Germany., Kaur S; Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, German Center for Infection Research (DZIF; Partner Site Giessen-Marburg-Langen), Justus Liebig University, 35392 Giessen, Germany., Möscheid MF; Institute of Parasitology, BFS, Justus Liebig University, 35392 Giessen, Germany., Haeberlein S; Institute of Parasitology, BFS, Justus Liebig University, 35392 Giessen, Germany., Grevelding CG; Institute of Parasitology, BFS, Justus Liebig University, 35392 Giessen, Germany., Weiskirchen R; Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, 52074 Aachen, Germany., El-Kassas M; Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo 11795, Egypt., Zalata K; Pathology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt., Roeb E; Department of Gastroenterology, Justus Liebig University, 35392 Giessen, Germany., Roderfeld M; Department of Gastroenterology, Justus Liebig University, 35392 Giessen, Germany. |
| Abstrakt: |
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. |
