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.


RESULTS
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
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.
Gottstein
Bruno
B
Vetsuisse Faculty, Institute of Parasitology, University of Bern, Bern, Switzerland. bruno.gottstein@ipa.unibe.ch
Wittwer
Matthias
M
Schild
Marc
M
Merli
Michael
M
Leib
Stephen L
SL
Müller
Norbert
N
Müller
Joachim
J
Jaggi
Rolf
R
D000818:Animals; D015415:Biomarkers; D004443:Echinococcosis / Q000276:immunology*; D048210:Echinococcus multilocularis / Q000276:immunology; D020869:Gene Expression Profiling / Q000295:instrumentation / Q000379:methods; D005786:Gene Expression Regulation / Q000276:immunology; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000378:metabolism / Q000469:parasitology*; D008107:Liver Diseases / Q000276:immunology / Q000469:parasitology; D051379:Mice; D010063:Ovum; D012333:RNA, Messenger / Q000032:analysis
D015415:Biomarkers; D012333:RNA, Messenger