PD Dr. Martina Sombetzki (Rostock / DE), Tomáš Macháček (Prague / CZ), Claudia D. Fuchs (Vienna / AT), Franziska Winkelmann (Rostock / DE), Michael Trauner (Vienna / AT)
Abstract text
Background & Objectives: Schistosoma mansoni infection is one of the worldwide leading causes of liver fibrosis and portal hypertension. The objective of this study was to evaluate whether polyhydroxylated bile acids, known to protect mice from development of acquired cholestatic liver injury, counteract Schistosoma mansoniinduced inflammation and fibrosis.
Materials & Methods: Adult FVB/N WT and Abcb11/Bsep KO mice were infected with either 25 or 50 Schistosoma mansoni cercariae. Eight weeks post infection, effects on liver histology, serum biochemistry, gene expression profile of pro-inflammatory cytokines and fibrotic markers, hepatic hydroxyproline content as well as FACS analysis were performed.
Results: Bsep KO mice infected with Schistosoma mansoni showed significantly less hepatic inflammation and tendentially less fibrosis compared to infected WT mice. Despite elevated ALT, AST, and AP levels in infected Bsep KO mice, inflammatory cells such as M2 macrophages and Mac-2/galectin-3+ cells were reduced in these animals. Accordingly, mRNA-expression levels of anti-inflammatory cytokines (IL-4; IL-13) were increased in Bsep KO mice upon infection. Furthermore, infected Bsep KO mice exhibited decreased hepatic egg load and parasite fecundity, consequently affecting the worm reproduction rate. Mechanistically these findings may at least in part be attributed to elevated serum bile acid levels and consecutively lower blood pH in infected Bsep KO mice.
Conclusions: The loss of Bsep and the resulting changes in bile acid composition and blood pH reduce parasite fecundity, thus attenuating development of S. mansoni induced hepatic inflammation and fibrosis.