Proteomic changes at 8 weeks after infection are associated with chronic liver pathology in experimental schistosomiasis

Chronic Schistosoma mansoni infection can present as a moderate or severe disease, termed intestinal or hepatosplenic schistosomiasis, respectively. Similarly, either moderate splenomegaly or hypersplenomegaly syndrome develops in CBA/J mice by 20 weeks of infection and is similar to intestinal or hepatosplenic schistosomiasis respectively. Using this mouse model and two-dimensional differential in gel electrophoresis, the liver proteomic signatures of uninfected mice and mice infected for 6, 8, 12, or 20 weeks were compared, and significant protein spots identified using mass spectrometry. We found the greatest number of changes at 12 weeks suggesting that this period represents the peak time of change. Pathway analysis identified specific proteins and pathways that correlated to the pathological changes indicative of severe disease, and these pathways were involved as early as 8 weeks after infection. These findings provide insight into the development of severe liver pathology in schistosomiasis and may aid in developing biomarkers for hepatosplenic schistosomiasis.

Graphical abstractUsing pathway analyses, we found that schistosome-infected mice that developed significant splenomegaly early during infection clustered with 20-week, hepatosplenic mice based upon proteomic liver signatures.Figure optionsDownload full-size imageDownload high-quality image (67 K)Download as PowerPoint slideHighlights► Liver proteomic profiles showed changes predictive of hepatosplenic disease occurred by 8 weeks post S. mansoni infection. ► The greatest number of protein changes occurred at 12 weeks suggesting this period represents the peak time of change. ► Pathway analysis revealed the potential involvement of the ESR1 network in the pathological changes during severe disease. ► This study identifies potential factors driving severe liver disease and may lead to new biomarkers for schistosomiasis.