Unknown,Transcriptomics,Genomics,Proteomics

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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 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.

ORGANISM(S): Mus musculus

SUBMITTER: Jose Rojas-Caraballo

PROVIDER: E-GEOD-69588 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Fasciolosis remains an important food-borne tremaode disease causing high morbidity around the world and affecting grazing animals and humans. A deeper understanding concerning the molecular mechanisms by which Fasciola hepatica infection occurs as well as the molecular basis involved in acquiring protection is extremely important in designing and selecting new vaccine candidates. The present study gives a first report of microarray-based technology for describing changes in splenic gene expression profile for mice immunised with a highly effective, protection-inducing,multi-epitope, subunit-based, chemically-synthesised vaccine candidate. Female CD1 mice were immunised with synthetic peptides containing B- and T-cell epitopes as novel vaccine candidates and challenged with Fasciola hepatica metacercariae. Spleen RNA from mice immunised with the highest protection-inducing synthetic peptides was isolated, amplified and labelled using Affymetrix standardised protocols. The Ingenuity Pathway Analysis tool was used to annotate bio-functions and constructing and visualising molecular interaction networks. Immunising mice with a combination of three peptides containing T-cell epitopes induced high protection against experimental challenge according to survival rates and hepatic damage scores. It also induced differential expression of 820 genes; 168 being up-regulated and 652 down-regulated. Functional study revealed changes in pathways related to nitric oxide and reactive oxygen species production, IL-12 signalling and production in macrophages and IL-8 signalling with up-regulation of S100A8, MMP9 and CXCR2 genes. The data obtained in the present study provided us with a more comprehensive overview concerning the possible molecular pathways implied in inducing protection against Fasciola hepatica in a murine model Three mice were used as healthy controls and remained untreated along the experiment. Three mice were subcutaneously immunised with our vaccine candidate on day 0, and two booster doses were applied on days 14 and 28, respectively. Two-weeks after the last immunisation, all of the mice used in the present study (including controls) were humanely euthanised by intraperitoneal injection of pentobarbital (60mg/Kg) and necropsied for spleen recovery and RNA isolation using standardised protocols. Splenic gene expression profile was compared between healthy and immunised groups.

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.

Project description:A first generation Affymetrix GeneChipÂ® Porcine genome array was used to profile the gene expression in porcine mesenteric lymph nodes over a time course of infection with S. Typhimurium, including the acute (8 hours post inoculation (hpi), 24 hpi, 48 hpi) and chronic (21 days post-inoculation (dpi)) stages of infection. Our objectives were to 1) identify and examine the stereotypical gene expression response within host MLN to S. Typhimurium infection, 2) characterize global host responses by revealing the specific features of the hostâs innate immunity pathways, and 3) explore if and how S. Typhimurium may escape the host immune response and develop into a carrier state. Our study has attempted to investigate the features of host gene expression profiling during S. Typhimurium infection at the acute and chronic infection stages and to explore the mechanism by which S. Typhimurium can escape from the host immune response and develop a carrier state in the host. In conclusion, by using the Affymetrix porcine GeneChip, 848 differentially expressed genes were identified in porcine MLN during infection and several specific features of host response were revealed by gene cluster and pathway analysis. Our data are the first report to investigate global host responses to S. Typhimurium in porcine MLN, and this new study provides data applicable for studying enteric salmonellosis of pigs, as well as humans. Experiment Overall Design: Fifteen piglets from Salmonella spp.-free sows were weaned at 10 days (d) of age, shipped to the National Animal Disease Center, Ames, IA and raised in isolation facilities. To confirm that all piglets were free of Salmonella spp. prior to challenge, bacteriological cultures were performed on rectal swabs twice. Seven week old pigs were randomly divided into 2 groups, 3 non-infected pigs and 12 infected pigs. Three non-infected control pigs were necropsied 2 days prior to experimental infection. On day 0, pigs in the infected groups were intranasally challenged with 1 billion CFU of Salmonella enterica serovar Typhimurium. Three infected pigs were necropsied at 8 hours post-inoculation (hpi), 24 hpi, 48 hpi and 21 days post-inoculation (dpi). Tissue samples from the mesenteric lymph nodes (MLN) were collected and immediately frozen in liquid nitrogen for RNA isolation.

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Gene expression profile in the liver of BALB/c mice infected with Fasciola hepatica

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