Abstract
BackgroundAlveolar 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 FindingsWe 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/SignificanceBased 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.
Highlights
Alveolar echinococcosis (AE) is a result of a hepatic infection with the larval stage of the fox tapeworm Echinococcus multilocularis
AE patients are affected by hepatic sequelae that are due to a wide spectrum of liver injury leading predominantly to cholestatic jaundice and/or unspecific epigastric pain, together with various symptoms such as fatigue, weight loss and hepatomegaly [2]
All mice were housed and handled under standard aseptic animal laboratory conditions according to the rules of the Swiss regulations for animal experimentation
Summary
Alveolar echinococcosis (AE) is a result of a hepatic infection with the larval (metacestode) stage of the fox tapeworm Echinococcus multilocularis. The real approach to determining the biological events in vivo is to carry out peroral inoculation of infectious E. multilocularis eggs, experiments that can only be performed in appropriate biosafety level 3 laboratory units Such experimental infection is referred to as primary infection, resulting in an intrahepatic tumor-like growth of the metacestode that overcomes the immune system and subsequently establishes a chronic phase of infection, which persists approximately between 4–6 months p.i. Through effects on cells of both the innate and adaptive arms of the immune response, the parasite can orchestrate a range of outcomes that are beneficial for metacestode establishment, and in terms of facilitating its proliferation and maturation. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
