Fasciola hepatica miRNAs in mouse peritoneal Ago2
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE145597 | GEO | 2020/02/21
REPOSITORIES: GEO
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Project description: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 Fasciola hepatica metacercariae using a microarray-based methodology. Methodology: A 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). Results: We found that Fasciola 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. Conclusion: The present study provides us insights at the molecular level about the underlying mechanisms used by Fasciola 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. We used three experimental groups each containing 3 mice. Group 1 remains untreated and served as control. Group 2 was infected with Fasciola hepatica metacercariae on day 0 and humanely necropsied at 7 days post-infection. Group 3 was infected with Fasciola hepatica metacercariae on day 0 and humanely necropsied at 21 days post- infection. At the time of necropsy, liver of each mice were removed and the RNA was isolated. We compared the gene expression profile in the liver of mice infected with Fasciola hepatica.
2015-06-05 | E-GEOD-69588 | biostudies-arrayexpress
Project description:Parasitic worms (helminths) ensure their survival to establish chronic infection within mammalian hosts by strategically regulating their host s immune responses. Deciphering the mechanisms behind this immune modulation will inform the development of novel strategies for infection control. It is now understood that the co-ordinated control of gene expression by non-coding RNAs (ncRNA) underpins the activation and regulation of immune cells. However, it is also clear that pathogens (including helminths) secrete their own ncRNAs to manipulate host gene expression and influence immune outcomes to infection. To discriminate the contribution of host and helminth derived ncRNAs to the activation and/or regulation of innate immune responses during infection, we examined ncRNA expression in the peritoneal macrophages from mice infected with Fasciola hepatica. This revealed an enrichment of several parasitic-derived miRNAs (fhe-miR-277b-3p, fhe-miR-71a-5p, fhe-miR-125b-5p, fhe-miR-125a-5p) within macrophages at 6hr and 18hr after infection which is coincident with the parasite s migration through the peritoneal cavity. Target prediction analysis indicated that these Fasciola miRNAs regulated host genes associated with the activation of host pro-inflammatory macrophages (Hif1 , Nod1, Nlrp6 and P2rx7). Concomitantly, there was a distinct shift in host ncRNA expression in response to infection, which was most significant at 5 days post-infection. Although, analysis suggested that these host ncRNAs target a different cohort of genes (Adar1, Igf1 and Plec) to the parasite miRNAs, the functional outcome was predicted to be the same, with a reduced pro-inflammatory response and the promotion of a reparative/tolerant phenotype. Combined, these observations uncover the interplay between host and parasitic ncRNAs and reveals a complementary regulation of the immune response that allows the parasite to evade immune detection and promotes tissue repair for the host. This level of characterisation of the ncRNA landscape during helminth infection is highly novel and provides a new understanding of the molecular impact that these parasites have on host immune cells.
2024-09-30 | GSE263895 | GEO
Project description:F. hepatica is a parasite causing losses of great importance in animal production. It is also considered a zoonosis of growing importance. During the infection the parasite releases a number of antigens (called Excretory Secretory Products - ESP) facilitating the parasites survival. A number of ESP components have immunomodulatory properties. To determine if ES from various F. hepatica isolates have different immunomodulatory abilities “BOMA” cells were stimulated with ES from laboratory Weybridge (FhWey-ES) and wild (FhWild-ES) Fasciola hepatica isolates.
2018-03-13 | GSE95019 | GEO
Project description:F. hepatica is a parasite causing losses of great importance in animal production. It is also considered a zoonosis of growing importance. During the infection the parasite releases a number of antigens (called Excretory Secretory Products - ESP) facilitating the parasites survival. A number of ESP components have immunomodulatory properties. To determine if ES from various F. hepatica isolates have different immunomodulatory abilities LPS activated “BOMA” cells were stimulated with ES of laboratory Weybridge (FhWey-ES) and wild (FhWild-ES) Fasciola hepatica isolates.
2017-11-01 | GSE95022 | GEO
Project description: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 Fasciola hepatica metacercariae using a microarray-based methodology. Methodology: A 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). Results: We found that Fasciola 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. Conclusion: The present study provides us insights at the molecular level about the underlying mechanisms used by Fasciola 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.
2015-06-05 | GSE69588 | GEO
Project description:The liver fluke Fasciola hepatica is an economically important pathogen of livestock. Fasciolosis in humans is an important re-emerging zoonosis, with 180 million people at risk. Development of novel control strategies requires an understanding of parasite virulence and tissue invasion, and of how the parasite evades and modulates the immune response during early infection. A combination of immunological and proteomic analyses was employed to investigate the peritoneal fluid of sheep infected with F. hepatica to characterise early tissue invasion and liver pathogenesis. At 18 days post-infection (dpi), histopathology of sheep liver showed white necrotic foci/tracts indicative of F. hepatica migration. Within the peritoneal fluid of infected animals, specific F. hepatica antigen FhCL1 antibodies coincided with an intense innate and adaptive cellular immune response, with increasing numbers of total leukocytes and a marked eosinophilia (49%). Cytokine qPCR analysis revealed IL-10, IL-12, IL-13, IL-23 and TGFβ were elevated but not statistically significant at 18 dpi compared to uninfected sheep indicating that whilst the immune response is developing it has not polarised to the Th2 type associated with chronic fasciolosis. Proteomic analysis of the peritoneal fluid identified 178 proteins, with 25 proteins more highly expressed in the infected animals, based on fold changes in protein concentration compared to the uninfected animals. Components of the liver extracellular matrix, including collagen, periostin and the adhesion protein, VCAM-1, exhibited increased expression associated with early fasciolosis, which may be important in signalling host immune responses to tissue damage. In early F. hepatica infection cellular infiltration with marked eosinophilia, adaptive immune responses and products of liver pathology are evident in the peritoneum. Although cytokine responses are developing they are mixed and not yet polarised to a Th2-type. We have characterised biomarkers of parasite-induced liver damage which could be exploited for diagnosis, and vaccine development aimed at reducing/preventing liver pathology.
2018-03-26 | PXD005548 | Pride
Project description:Background The parasite Fasciola hepatica infects a broad range of mammals with impunity. Following ingestion of parasites (metacercariae) by the host, newly excysted juveniles (NEJ) emerge from their cysts, rapidly penetrate the duodenal wall and migrate to the liver. Successful infection takes just a few hours and involves negotiating hurdles presented by host macromolecules, tissues and micro-environments, as well as the immune system. Results Transcriptome and proteome analysis of F. hepatica metacercariae and NEJ revealed the rapidity and multitude of metabolic and developmental alterations this parasite undergoes to accomplish infection. We show that metacercariae are metabolically active, contrary to the view that this stage is dormant. Following ingestion, the NEJ expend vital energy stores and rapidly adjust their metabolic pathways to cope with their new increasingly anaerobic environment. Temperature increases induce neoblast proliferation and the remarkable up-regulation of genes associated with growth and development. Cysteine proteases synthesised by gastrodermal cells are secreted to facilitate invasion and tegumental transporters are varied to deal with osmotic/salinity changes. Major proteins of the total NEJ secretome include proteases, proteases inhibitors, anti-oxidants as well as an array of immunomodulators that likely disarm host innate immune effector cells. Conclusions The challenges of infection by F. hepatica parasites are met by rapid metabolic and physiological adjustments that expedite tissue invasion and immune evasion that facilitate growth, development and maturation. Our molecular analysis of the critical process of host invasion has identified key targets for future drug and vaccine strategies directed at preventing parasite infection.
2018-03-26 | PXD007255 | Pride
Project description:Liver fluke (Fasciola hepatica) infection is both a welfare and productivity issue in sheep farming. Death can result from acute infection, and deaths are becoming more frequent as anthelmintic resistance increases. New control strategies are desirable, and vaccination is a good option. Previous studies have shown an experimental vaccine based on a F. hepatica protein, cathepsin L1, (rmFhCL1) may be a viable aid to control liver fluke in cattle/sheep, however efficacy is variable. A trial was conducted on sheep immunized with rmFhCL1 following infection with F. hepatica to understand the immune response changes induced by vaccinination at a molecular level . Peripheral blood mononuclear cells (PBMCs) were isolated at four different time points for RNA-Seq analysis. Genes differentially expressed between vaccinated and control animals were identified. Their functional roles were studied using in silico methods.
2016-11-04 | GSE71431 | GEO
Project description:The major pathogenesis associated with Fasciola hepatica infection results from the extensive tissue damage caused by the tunnelling and feeding activity of immature flukes during their migration, growth and development in the liver. This is compounded by the pathology caused by host innate and adaptive immune responses that struggle to repair this damage. Complementary transcriptomic and proteomic approaches defined the F. hepatica factors associated with their migration in the liver, and the resulting immune-pathogenesis. The liver-stage parasites display different secretome profiles, reflecting their distinct niche within the host, and supports the view that cathepsin peptidases, cathepsin peptidase inhibitors, saposins and leucine aminopeptidases play a central role in the parasite’s destructive migration, digest of host tissue and blood. Immature flukes are also primed for countering immune attack by secreting immunomodulating fatty acid binding proteins (FABP) and helminth defense molecules (FhHDM). The migration of immature F. hepatica parasites within the liver is associated with an increase in protein production, expression of signalling pathways and neoblast proliferation that drive their rapid growth and development. The secretion of a defined set of molecules, particularly cathepsin L peptidases, peptidase-inhibitors, saponins, immune-regulators and anti-oxidants allow the parasite to negotiate the liver micro-environment, immune attack and increasing levels of oxidative stress. This data contributes to the growing F. hepatica -omics information that can be exploited to understand parasite development more fully and for the design of novel control strategies to prevent host liver tissue destruction and pathology.
2021-09-09 | PXD021221 | Pride