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

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.

Differential expressions of MHC-DQB1 mRNA in Chinese merino sheep infected with Echinococosus granuclosus

“…Compared with group A, DQB1 mRNA in group B showed a higher expression level from day 0 to day 21 post-infection. Similar data were obtained by Gottstein et al (2010), who found that the expression levels of genes within MHC class II were higher in mock-infected mice (healthy controls) than that in alveolar echinococcosis (AE) infection mice in the early stage of infection, stating that genes within MHC implicated in the immunopathophysilogical mechanisms leading to the induction of a host response to infection. Interestingly, on day 7 post-infection, DQB1 mRNA expression level in group B was significantly higher than that in group A (67.98±27.23 vs. 15.20±1.90, P00.002), suggesting that a strong immune response associated with MHC occurred within the first week post-infection-which may be due to the fact that at the early phase of E. granuclosus infection, antigens secreted by E. granuclosus could be capable of stimulating the expression of DQB1 mRNA strongly, thus triggering a marked activation of cellmediated immunity within the first week.…”

Susceptibility versus resistance in alveolar echinococcosis (larval infection with Echinococcus multilocularis)

“…Principally, FGL2 is a member of the fibrinogen-related superfamily of proteins secreted by T cells, is highly expressed in Tregs, and has an important role in Treg cell effector function (Levy et al, 2000). Micro-array studies showed that FGL2 expression is significantly up-regulated in the liver of E. multilocularis-infected mice (Gottstein et al, 2011). Upon use of E. multilocularis-infected fgl2-deficient mice (as compared to infected WT mice), a significantly lower parasite load and a reduced proliferation activity was observed, associated with increased T cell proliferation in response to ConA, reduced Treg numbers and function, relative Th1 polarisation, and increased B cell numbers and DC maturation (Wang et al, 2015).…”

Recent Advances in the Immunology and Serological Diagnosis of Echinococcosis

“…There is an urgent need for the early diagnosis. The application of new techniques is a way to address these issues; for example, recent microarray analysis identified 5 genes (Gapdh, Est1, Rlp3, Mdh-1, Rpl37) exhibiting a high level of congruency, and these may provide new diagnostic targets to predict disease status and progression (Gottstein et al, 2010).…”