Gene Expression Profile in the Liver of BALB/c Mice Infected with Fasciola hepatica

Abstract

Background Fasciola hepatica infection still remains one of the helminthic neglected tropical diseases (NTDs). It has a huge worldwide distribution, affecting mainly cattle and, sometimes, human beings. In addition to data reported about the immunological response induced by helminthic infections and that induced by Fasciola hepatica, little is known about the gene expression profile in its organ target, the liver, which is where adult worms are established and live for long periods of time, causing its characteristic pathology. In the present work, we study both the early and late gene expression profiles in the livers of mice infected with F. hepatica metacercariae using a microarray-based methodology.MethodologyA total of 9 female-6-week-old BALB/c mice (Charles River Laboratories, Barcelona, Spain) weighing 20 to 35 g were used for the experiments. Two groups of BALB/c mice were orally infected with seven F. hepatica metacercariae, and the other group remained untreated and served as a control. Mice were humanely euthanized and necropsied for liver recovery, histological assessment of hepatic damage, RNA isolation, microarray design and gene expression analysis on the day of infection (t0), seven days post-infection (t7) and twenty-one days post-infection (t21).ResultsWe found that F. hepatica infection induces the differential expression of 128 genes in the liver in the early stage of infection and 308 genes in the late stage, and most of them are up-regulated. The Ingenuity Pathway Analysis revealed significant changes in the pathways related to metabolism, biosynthesis and signaling as well as genes implicated in inducing liver-toxicity, injury and death.ConclusionThe present study provides us insights at the molecular level about the underlying mechanisms used by F. hepatica, leading to liver damage and its subsequent pathophysiology. The expression pattern obtained here could also be used to explain the lack of association between infection with F. hepatica and cholangiocarcinoma. However, more studies should be performed to confirm this hypothesis.

Advances in Fasciola hepatica research using ‘omics’ technologies

“…Transcriptomic responses within macroscopic lesions of F. hepatica-infected liver at 8 weeks post infection (wpi) in sheep revealed that gene expression is highly regulated (Alvarez Rojas et al, 2015), consistent with comparable microarray studies of mice (Rojas-Caraballo et al, 2015). Several processes characteristic of acute fasciolosis and upregulated in response to the damage caused by the parasite were identified.…”

The immune modulatory peptide FhHDM‐1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages

“…The resultant uncontrolled and excessive production of IL‐1κ mediates several proinflammatory disorders with severe pathologic outcomes (37). The migration of F. he‐ patica through the host's liver results in significant tissue damage (38, 39), and the parasite's secretions can induce hepatocyte cell death (40, 41). Inflammation and fibrosis in the liver is typically associated with excessive NLRP3 inflammasome activity, culminating in hepatocyte destruction via pyroptosis and IL‐1β secretion (42).…”

“…Such outcomes lead to sustained activation of proinflammatory immune responses (34) and mediate pathologic events, such as TNF-induced cell death (42). However, the expression of genes involved in both the IFN and TNF signaling pathways is actually reduced in F. hepatica-infected liver tissue (38), and lysosomal cathepsin B activity is diminished (43). These observations imply that the NLRP3 inflammasome is not activated during F. hepatica infection.…”

Time-course investigation of the gene expression profile during Fasciola hepatica infection: A microarray-based study

“…We investigated the gene expression profile during early and late stages of Fasciola hepatica infection in BALB/c mice [1] . For this purpose, we have selected three experimental groups, each containing 3 mice.…”

“…Data presented here belong to a time-course investigation of the gene expression profile in the liver of BALB/c mice infected with F. hepatica metacercariae at 7 and 21 days after experimental infection. The data published here have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE69588 , previously published by Rojas-Caraballo et al (2015) in PLoS One [1] .…”