Hepatic Gene Expression Profile in Mice Perorally Infected with Echinococcus multilocularis Eggs

Background: Alveolar echinococcosis (AE) is a severe chronic hepatic parasitic disease currently emerging in central and eastern Europe. Untreated AE presents a high mortality (>90%) due to a severe hepatic destruction as a result of parasitic metacestode proliferation which behaves like a malignant tumor. Despite this severe course and outcome of disease, the genetic program that regulates the host response leading to organ damage as a consequence of hepatic alveolar echinococcosis is largely unknown. Methodology/Principal Findings: We used a mouse model of AE to assess gene expression profiles in the liver after establishment of a chronic disease status as a result of a primary peroral infection with eggs of the fox tapeworm Echinococcus multilocularis. Among 38 genes differentially regulated (false discovery rate adjusted p <= 0.05), 35 genes were assigned to the functional gene ontology group < immune response >, while 3 associated with the functional group < intermediary metabolism >. Upregulated genes associated with, immune response. could be clustered into functional subgroups including < macrophages >, < APCs >, < lymphocytes, chemokines and regulation >, < B-cells > and < eosinophils >. Two downregulated genes related to < lymphocytes, chemokines and regulation > and < intermediary metabolism >, respectively. The < immune response > genes either associated with an < immunosupression > or an < immunostimulation > pathway. From the overexpressed genes, 18 genes were subsequently processed with a Custom Array microfluidic card system in order to assess respective expression status at the mRNA level relative to 5 reference genes (Gapdh, Est1, Rlp3, Mdh-1, Rpl37) selected upon a constitutive and stable expression level. The results generated by the two independent tools used for the assessment of gene expression, i.e., microarray and microfluidic card system, exhibited a high level of congruency (Spearman correlation rho = 0.81, p = 7.87e-5) and thus validated the applied methods. Conclusions/Significance: Based on this set of biomarkers, new diagnostic targets have been made available to predict disease status and progression. These biomarkers may also offer new targets for immuno-therapeutic intervention.