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Banchob Sripa - One of the best experts on this subject based on the ideXlab platform.

  • Predictive risk factors towards Liver Fluke infection among the people in Kamalasai District, Kalasin Province, Thailand.
    SAGE open medicine, 2019
    Co-Authors: Woragon Wichaiyo, Wirat Parnsila, Wisit Chaveepojnkamjorn, Banchob Sripa
    Abstract:

    Background Liver Fluke disease caused by Opisthorchis viverrini remains a major public health problem with its crucial risk factors caused by some individual habits or false beliefs among the people in northeastern Thailand concerning the consumption of raw fish meat dishes. Objectives This study explores the predictive risk factors for the infection of Liver Fluke disease. Methods The sample consisted of 400 people aged 30 years and above in Thanya sub-district, Kamalasai district, Kalasin province. A cross-sectional analytic study, using the χ2 test, odds ratio and 95% confidence interval, was used to find the influence of each variable, along with the use of multiple logistic regression (p = 0.05). A questionnaire form was used as the research instrument. Results Factors found in the results are as follows: households with a cat were 7.00 times more at risk than households without a cat; eating raw fish dishes prepared by themselves increases the risk of infection by 2.58 times; eating raw fish dishes prepared by family members increases the risk by 4.74 times; and raw fish dishes bought from a community market increases the risk by 2.33 times. Conclusion A campaign should be launched to educate people not to eat raw or undercooked fish dishes, but to fully cook fish dishes before eating, as the food is still delicious, but also safe, healthy, and free from Liver Fluke infection.

  • programmed knockout mutation of Liver Fluke granulin attenuates virulence of infection induced hepatobiliary morbidity
    eLife, 2019
    Co-Authors: Michael J. Smout, Patpicha Arunsan, Christina J Cochran, Shannon E Karinshak, Banchob Sripa, Victoria H. Mann, Wannaporn Ittiprasert, Sujittra Chaiyadet, Neil D. Young
    Abstract:

    Infection with the food-borne Liver Fluke Opisthorchis viverrini is the principal risk factor (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2012) for cholangiocarcinoma (CCA) in the Lower Mekong River Basin countries including Thailand, Lao PDR, Vietnam and Cambodia. We exploited this link to explore the role of the secreted growth factor termed Liver Fluke granulin (Ov-GRN-1) in pre-malignant lesions by undertaking programmed CRISPR/Cas9 knockout of the Ov-GRN-1 gene from the Liver Fluke genome. Deep sequencing of amplicon libraries from genomic DNA of gene-edited parasites revealed Cas9-catalyzed mutations within Ov-GRN-1. Gene editing resulted in rapid depletion of Ov-GRN-1 transcripts and the encoded Ov-GRN-1 protein. Gene-edited parasites colonized the biliary tract of hamsters and developed into adult Flukes, but the infection resulted in reduced pathology as evidenced by attenuated biliary hyperplasia and fibrosis. Not only does this report pioneer programmed gene-editing in parasitic flatworms, but also the striking, clinically-relevant pathophysiological phenotype confirms the role for Ov-GRN-1 in virulence morbidity during opisthorchiasis.

  • modeling Liver Fluke transmission in northeast thailand impacts of development hydrology and control
    Acta Tropica, 2018
    Co-Authors: Sasithorn Kaewkes, Banchob Sripa, Tomas Leon, Travis C Porco, Christina Sunyoung Kim, Wanlop Kaewkes, Robert C Spear
    Abstract:

    Human infection with the Southeast Asian Liver Fluke Opisthorchis viverrini and Liver Fluke-associated cholangiocarcinoma cause significant disease burden in Southeast Asia. While there has been considerable work to understand Liver Fluke pathology and to reduce infection prevalence, there remains a limited understanding of the environmental determinants of parasite transmission dynamics to inform treatment and control programs. A particular setting where targeted control efforts have taken place is the Lawa Lake complex in northeast Thailand. Here, we describe the recent history of host infections, as well as the hydrologic characteristics of this floodplain ecosystem that influence the extent of snail habitat and fish mobility and the transport of human waste and parasite cercariae. Using mathematical modeling, we outline a framework for reconstructing environmental transmission of O. viverrini over the course of the Lawa Project control program from its inception in 2008 until 2016, using locally acquired but fragmentary longitudinal infection data for both humans and environmental hosts. The role of water flow in facilitating movement between snail, fish, human, and reservoir hosts is a particular focus with respect to its relevant scales and its impact on success of interventions. In this setting, we argue that an understanding of the key environmental drivers of disease transmission processes is central to the effectiveness of any environmental intervention.

  • programmed mutation of Liver Fluke granulin using crispr cas9 attenuates virulence of infection induced hepatobiliary morbidity
    bioRxiv, 2018
    Co-Authors: Patpicha Arunsan, Michael J. Smout, Christina J Cochran, Shannon E Karinshak, Banchob Sripa, Victoria H. Mann, Neil D. Young, Wannaporn Ittiprasert, Sujittra Chaiyadet, Javier Sotillo
    Abstract:

    Infections with several flatworm parasites represent group 1 biological carcinogens, i.e. definite causes of cancer. Infection with the food-borne Liver Fluke Opisthorchis viverrini causes cholangiocarcinoma (CCA). Whereas the causative agent for most cancers, including CCA in the West, remains obscure, the principal risk factor for CCA in Thailand is opisthorchiasis. We exploited this established link to explore the role of the secreted parasite growth factor termed Liver Fluke granulin (Ov-GRN-1) in pre-malignant lesions of the biliary tract. We targeted the Ov-grn-1 gene for programmed knockout and investigated gene-edited parasites in vitro and in experimentally infected hamsters. Both adult and juvenile stages of the Liver Fluke were transfected with a plasmid encoding a guide RNA sequence specific for exon 1 of Ov-grn-1 and the Cas9 nuclease. Deep sequencing of amplicon libraries from genomic DNA from gene-edited parasites exhibited programmed, Cas9-catalyzed mutations within the Ov-grn-1 locus, and tandem analyses by RT-PCR and western blot revealed rapid depletion of Ov-grn-1 transcripts and protein. Newly excysted juvenile Flukes that had undergone editing of Ov-grn-1 colonized the biliary tract, grew and developed over a period of 60 days, were active and motile, and induced a clinically relevant pathophysiological tissue phenotype of attenuated biliary hyperplasia and fibrosis in comparison to infection with wild type Flukes. This is the first report of gene knock-out using CRISPR/Cas9 in a parasitic flatworm, demonstrating the activity and utility of the process for functional genomics in these pathogens. The striking clinical phenotype highlights the role in virulence that Liver Fluke growth factors play in biliary tract morbidity during chronic opisthorchiasis.

  • Social Influence in Liver Fluke Transmission: Application of Social Network Analysis of Food Sharing in Thai Isaan Culture
    Advances in parasitology, 2018
    Co-Authors: Waraphon Phimpraphai, Sirikachorn Tangkawattana, Suwicha Kasemsuwan, Banchob Sripa
    Abstract:

    In northeastern Thai (Isaan) culture traditional raw fish dishes and raw fish-eating habits are common. Eating and sharing meals together among the community's members, especially relatives and neighbours, are a common practice in both daily life and social gathering events. Fish are a significant protein source and are associated with variety of traditional recipes. Cyprinid fish are one of the most preferred fish by Isaan villagers for daily consumption because they are accessible and affordable. Consumption of these fish probably causes the persistence of high endemicity of human Liver Fluke infection, particularly with Opisthorchis viverrini, in northeast Thailand. Because the consumption of raw cyprinid fish is a well-documented risk factor for Liver Fluke infection, sharing of risky raw fish dishes may influence disease transmission through a community. Social network analysis was used to investigate fish and fish-based meal sharing among household members in Isaan villages in Liver Fluke endemic areas. The findings from three studies confirmed the persistence of traditional Isaan raw fish consumption and food-sharing practice. Social connections via food sharing among villagers played an important role in Liver Fluke infection and transmission dynamics as a risk factor. Thus these sociocultural factors should be taken into account in designing strategies for control of opisthorchiasis and other food-borne illnesses at the community level.

Michael J. Smout - One of the best experts on this subject based on the ideXlab platform.

  • Liver Fluke granulin promotes extracellular vesicle mediated crosstalk and cellular microenvironment conducive to cholangiocarcinoma
    Neoplasia, 2020
    Co-Authors: Michael J. Smout, Patpicha Arunsan, Apisit Chaidee, Christina J Cochran, Chutima Kumkhaek, Victoria H. Mann, Toshihiko Tanno, Shannon E Karinshak
    Abstract:

    Abstract Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with the Liver Fluke is a major risk factor for cholangiocarcinoma (CCA). The Liver Fluke Opisthorchis viverrini secretes a growth factor termed Liver Fluke granulin, a homologue of the human progranulin, which contributes significantly to biliary tract fibrosis and morbidity. Here, extracellular vesicle (EV)-mediated transfer of mRNAs from human cholangiocytes to naive recipient cells was investigated following exposure to Liver Fluke granulin. To minimize the influence of endogenous progranulin, its cognate gene was inactivated using CRISPR/Cas9-based gene knock-out. Several progranulin-depleted cell lines, termed ΔhuPGRN-H69, were established. These lines exhibited >80% reductions in levels of specific transcript and progranulin, both in gene-edited cells and within EVs released by these cells. Profiles of extracellular vesicle RNAs (evRNA) from ΔhuPGRN-H69 for CCA-associated characteristics revealed a paucity of transcripts for estrogen- and Wnt-signaling pathways, peptidase inhibitors and tyrosine phosphatase related to cellular processes including oncogenic transformation. Several CCA-specific evRNAs including MAPK/AKT pathway members were induced by exposure to Liver Fluke granulin. By comparison, estrogen, Wnt/PI3K and TGF signaling and other CCA pathway mRNAs were upregulated in wild type H69 cells exposed to Liver Fluke granulin. Of these, CCA-associated evRNAs modified the CCA microenvironment in naive cells co-cultured with EVs from ΔhuPGRN-H69 cells exposed to Liver Fluke granulin, and induced translation of MAPK phosphorylation related-protein in naive recipient cells in comparison with control recipient cells. Exosome-mediated crosstalk in response to Liver Fluke granulin promoted a CCA-specific program through MAPK pathway which, in turn, established a CCA-conducive disposition.

  • programmed knockout mutation of Liver Fluke granulin attenuates virulence of infection induced hepatobiliary morbidity
    eLife, 2019
    Co-Authors: Michael J. Smout, Patpicha Arunsan, Christina J Cochran, Shannon E Karinshak, Banchob Sripa, Victoria H. Mann, Wannaporn Ittiprasert, Sujittra Chaiyadet, Neil D. Young
    Abstract:

    Infection with the food-borne Liver Fluke Opisthorchis viverrini is the principal risk factor (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2012) for cholangiocarcinoma (CCA) in the Lower Mekong River Basin countries including Thailand, Lao PDR, Vietnam and Cambodia. We exploited this link to explore the role of the secreted growth factor termed Liver Fluke granulin (Ov-GRN-1) in pre-malignant lesions by undertaking programmed CRISPR/Cas9 knockout of the Ov-GRN-1 gene from the Liver Fluke genome. Deep sequencing of amplicon libraries from genomic DNA of gene-edited parasites revealed Cas9-catalyzed mutations within Ov-GRN-1. Gene editing resulted in rapid depletion of Ov-GRN-1 transcripts and the encoded Ov-GRN-1 protein. Gene-edited parasites colonized the biliary tract of hamsters and developed into adult Flukes, but the infection resulted in reduced pathology as evidenced by attenuated biliary hyperplasia and fibrosis. Not only does this report pioneer programmed gene-editing in parasitic flatworms, but also the striking, clinically-relevant pathophysiological phenotype confirms the role for Ov-GRN-1 in virulence morbidity during opisthorchiasis.

  • structural variants of a Liver Fluke derived granulin peptide potently stimulate wound healing
    Journal of Medicinal Chemistry, 2018
    Co-Authors: Mohadeseh Dastpeyman, Michael J. Smout, Paramjit S Bansal, Javier Sotillo, Paul J Brindley, Alex Loukas, David Wilson, Norelle L Daly
    Abstract:

    Granulins are a family of growth factors involved in cell proliferation. The Liver-Fluke granulin, Ov-GRN-1, isolated from a carcinogenic Liver Fluke Opisthorchis viverrini, can significantly accelerate wound repair in vivo and in vitro. However, it is difficult to express Ov-GRN-1 in recombinant form at high yield, impeding its utility as a drug lead. Previously we reported that a truncated analogue (Ov-GRN12–35_3s) promotes healing of cutaneous wounds in mice. NMR analysis of this analogue indicates the presence of multiple conformations, most likely as a result of proline cis/trans isomerization. To further investigate whether the proline residues are involved in adopting the multiple confirmations, we have synthesized analogues involving mutation of the proline residues. We have shown that the proline residues have a significant influence on the structure, activity, and folding of Ov-GRN12–35_3s. These results provide insight into improving the oxidative folding yield and bioactivity of Ov-GRN12–35_3s...

  • programmed mutation of Liver Fluke granulin using crispr cas9 attenuates virulence of infection induced hepatobiliary morbidity
    bioRxiv, 2018
    Co-Authors: Patpicha Arunsan, Michael J. Smout, Christina J Cochran, Shannon E Karinshak, Banchob Sripa, Victoria H. Mann, Neil D. Young, Wannaporn Ittiprasert, Sujittra Chaiyadet, Javier Sotillo
    Abstract:

    Infections with several flatworm parasites represent group 1 biological carcinogens, i.e. definite causes of cancer. Infection with the food-borne Liver Fluke Opisthorchis viverrini causes cholangiocarcinoma (CCA). Whereas the causative agent for most cancers, including CCA in the West, remains obscure, the principal risk factor for CCA in Thailand is opisthorchiasis. We exploited this established link to explore the role of the secreted parasite growth factor termed Liver Fluke granulin (Ov-GRN-1) in pre-malignant lesions of the biliary tract. We targeted the Ov-grn-1 gene for programmed knockout and investigated gene-edited parasites in vitro and in experimentally infected hamsters. Both adult and juvenile stages of the Liver Fluke were transfected with a plasmid encoding a guide RNA sequence specific for exon 1 of Ov-grn-1 and the Cas9 nuclease. Deep sequencing of amplicon libraries from genomic DNA from gene-edited parasites exhibited programmed, Cas9-catalyzed mutations within the Ov-grn-1 locus, and tandem analyses by RT-PCR and western blot revealed rapid depletion of Ov-grn-1 transcripts and protein. Newly excysted juvenile Flukes that had undergone editing of Ov-grn-1 colonized the biliary tract, grew and developed over a period of 60 days, were active and motile, and induced a clinically relevant pathophysiological tissue phenotype of attenuated biliary hyperplasia and fibrosis in comparison to infection with wild type Flukes. This is the first report of gene knock-out using CRISPR/Cas9 in a parasitic flatworm, demonstrating the activity and utility of the process for functional genomics in these pathogens. The striking clinical phenotype highlights the role in virulence that Liver Fluke growth factors play in biliary tract morbidity during chronic opisthorchiasis.

  • granulin secreted by the food borne Liver Fluke opisthorchis viverrini promotes angiogenesis in human endothelial cells
    Frontiers in Medicine, 2018
    Co-Authors: Shannon E Karinshak, Brandon Haugen, Anastas Popratiloff, Victoria H. Mann, Paul J Brindley, Alex Loukas, Michael J. Smout
    Abstract:

    The Liver Fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent counties in Southeast Asia. The adult developmental stage of the O viverrini parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caused by the feeding activities of the Liver Fluke represent wounds that undergo protracted cycles of healing and re-injury over during chronic infection, which can last for decades. Components of the excretory/secretory (ES) complement released by the worms capably drive proliferation of bile duct epithelial cells and are implicated in establishing the oncogenic milieu that leads to bile duct cancer, cholangiocarcinoma (CCA). An ES protein, the secreted granulin-like growth factor termed Ov-GRN-1, accelerates wound resolution in mice and in vitro. To investigate angiogenesis (blood vessel development) that may contribute to wound healing promoted by Liver Fluke granulin and, by implication, to carcinogenesis during chronic opisthorchiasis, we employed an in vitro tubule formation assay (TFA) where human umbilical vein endothelial cells were grown on gelled basement matrix. Ten and 40 nM Ov-GRN-1 significantly stimulated angiogenesis as monitored by cellular proliferation and by TFA in real time. This demonstration of potent angiogenic property of Ov-GRN-1 bolsters earlier reports on the therapeutic potential for chronic non-healing wounds of diabetics, tobacco users, and the elderly and, in addition, showcases another of the hallmark of cancer characteristic of this carcinogenic Liver Fluke.

David Piedrafita - One of the best experts on this subject based on the ideXlab platform.

  • resistance to Liver Fluke infection in the natural sheep host is correlated with a type 1 cytokine response
    Parasite Immunology, 2011
    Co-Authors: Jill Louise Pleasance, Ening Wiedosari, Herman W. Raadsma, Elza Nicole Theresia Meeusen, David Piedrafita
    Abstract:

    Summary Indonesian thin-tail (ITT) sheep can resist infection with Fasciola gigantica but not F. hepatica and presents an ideal model to investigate the mechanisms of Liver Fluke resistance in a natural host. This study examines the local and systemic immune responses of sheep during Fasciola infection and demonstrates that different anatomical tissues display distinct cytokine profiles consistent with Liver Fluke migration. The study also reveals a significant difference in the cytokine and antibody profiles of ITT sheep infected with F. gigantica compared with F. hepatica, with a higher ratio of IL-4/IFN-γ mRNA expression and specific IgG1/IgG2 antibodies strongly correlating with pathology. Interestingly, the significant type-1 cytokine profile occurred in the lymph node closest to the site of infection at a time when the effective immune response against F. gigantica Liver Flukes is thought to occur. When the same F. gigantica infection in the resistant ITT sheep was compared with the susceptible Merino breed, the resistant type-1 phenotype against Liver Fluke infection was only observed in the ITT sheep. These studies provide the first evidence to suggest that the induction of an early type-1 immune response in this natural sheep host may be responsible for the ability to resist Liver Fluke infection.

  • Resistance to Liver Fluke infection in the natural sheep host is correlated with a type‐1 cytokine response
    Parasite immunology, 2011
    Co-Authors: Jill Louise Pleasance, Ening Wiedosari, Herman W. Raadsma, Elza Nicole Theresia Meeusen, David Piedrafita
    Abstract:

    Summary Indonesian thin-tail (ITT) sheep can resist infection with Fasciola gigantica but not F. hepatica and presents an ideal model to investigate the mechanisms of Liver Fluke resistance in a natural host. This study examines the local and systemic immune responses of sheep during Fasciola infection and demonstrates that different anatomical tissues display distinct cytokine profiles consistent with Liver Fluke migration. The study also reveals a significant difference in the cytokine and antibody profiles of ITT sheep infected with F. gigantica compared with F. hepatica, with a higher ratio of IL-4/IFN-γ mRNA expression and specific IgG1/IgG2 antibodies strongly correlating with pathology. Interestingly, the significant type-1 cytokine profile occurred in the lymph node closest to the site of infection at a time when the effective immune response against F. gigantica Liver Flukes is thought to occur. When the same F. gigantica infection in the resistant ITT sheep was compared with the susceptible Merino breed, the resistant type-1 phenotype against Liver Fluke infection was only observed in the ITT sheep. These studies provide the first evidence to suggest that the induction of an early type-1 immune response in this natural sheep host may be responsible for the ability to resist Liver Fluke infection.

Alex Loukas - One of the best experts on this subject based on the ideXlab platform.

  • structural variants of a Liver Fluke derived granulin peptide potently stimulate wound healing
    Journal of Medicinal Chemistry, 2018
    Co-Authors: Mohadeseh Dastpeyman, Michael J. Smout, Paramjit S Bansal, Javier Sotillo, Paul J Brindley, Alex Loukas, David Wilson, Norelle L Daly
    Abstract:

    Granulins are a family of growth factors involved in cell proliferation. The Liver-Fluke granulin, Ov-GRN-1, isolated from a carcinogenic Liver Fluke Opisthorchis viverrini, can significantly accelerate wound repair in vivo and in vitro. However, it is difficult to express Ov-GRN-1 in recombinant form at high yield, impeding its utility as a drug lead. Previously we reported that a truncated analogue (Ov-GRN12–35_3s) promotes healing of cutaneous wounds in mice. NMR analysis of this analogue indicates the presence of multiple conformations, most likely as a result of proline cis/trans isomerization. To further investigate whether the proline residues are involved in adopting the multiple confirmations, we have synthesized analogues involving mutation of the proline residues. We have shown that the proline residues have a significant influence on the structure, activity, and folding of Ov-GRN12–35_3s. These results provide insight into improving the oxidative folding yield and bioactivity of Ov-GRN12–35_3s...

  • granulin secreted by the food borne Liver Fluke opisthorchis viverrini promotes angiogenesis in human endothelial cells
    Frontiers in Medicine, 2018
    Co-Authors: Shannon E Karinshak, Brandon Haugen, Anastas Popratiloff, Victoria H. Mann, Paul J Brindley, Alex Loukas, Michael J. Smout
    Abstract:

    The Liver Fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent counties in Southeast Asia. The adult developmental stage of the O viverrini parasite excretes and secretes numerous proteins within the biliary tract including the gall bladder. Lesions caused by the feeding activities of the Liver Fluke represent wounds that undergo protracted cycles of healing and re-injury over during chronic infection, which can last for decades. Components of the excretory/secretory (ES) complement released by the worms capably drive proliferation of bile duct epithelial cells and are implicated in establishing the oncogenic milieu that leads to bile duct cancer, cholangiocarcinoma (CCA). An ES protein, the secreted granulin-like growth factor termed Ov-GRN-1, accelerates wound resolution in mice and in vitro. To investigate angiogenesis (blood vessel development) that may contribute to wound healing promoted by Liver Fluke granulin and, by implication, to carcinogenesis during chronic opisthorchiasis, we employed an in vitro tubule formation assay (TFA) where human umbilical vein endothelial cells were grown on gelled basement matrix. Ten and 40 nM Ov-GRN-1 significantly stimulated angiogenesis as monitored by cellular proliferation and by TFA in real time. This demonstration of potent angiogenic property of Ov-GRN-1 bolsters earlier reports on the therapeutic potential for chronic non-healing wounds of diabetics, tobacco users, and the elderly and, in addition, showcases another of the hallmark of cancer characteristic of this carcinogenic Liver Fluke.

  • Infection with the carcinogenic human Liver Fluke, Opisthorchis viverrini
    Molecular bioSystems, 2011
    Co-Authors: Michael J. Smout, Thewarach Laha, Banchob Sripa, Paul J Brindley, Jason Mulvenna, Robin B. Gasser, Neil D. Young, Jeffrey M. Bethony, Alex Loukas
    Abstract:

    Throughout Southeast Asia there is a strikingly high incidence of cholangiocarcinoma (CCA—hepatic cancer of the bile duct epithelium), particularly in people from rural settings in Laos and Northeast Thailand who are infected with the Liver Fluke, Opisthorchis viverrini, one of only three carcinogenic eukaryotic pathogens. More ubiquitous carcinogenic microbes, such as Helicobacter pylori, induce cancer in less than 1% of infected people, while as many as one-sixth of people with opisthorchiasis will develop CCA. The mechanisms by which O. viverrini causes cancer are multi-factorial, involving mechanical irritation from the activities and movements of the Flukes, immunopathology, dietary nitrosamines and the secretion of parasite proteins that promote a tumourigenic environment. Genomic and proteomic studies of the Liver Fluke secretome have accelerated the discovery of parasite proteins with known/potential roles in pathogenesis and tumourigenesis, establishing a framework towards understanding, and ultimately preventing, the morbidity and mortality attributed to this highly carcinogenic parasite.

Jill Louise Pleasance - One of the best experts on this subject based on the ideXlab platform.

  • resistance to Liver Fluke infection in the natural sheep host is correlated with a type 1 cytokine response
    Parasite Immunology, 2011
    Co-Authors: Jill Louise Pleasance, Ening Wiedosari, Herman W. Raadsma, Elza Nicole Theresia Meeusen, David Piedrafita
    Abstract:

    Summary Indonesian thin-tail (ITT) sheep can resist infection with Fasciola gigantica but not F. hepatica and presents an ideal model to investigate the mechanisms of Liver Fluke resistance in a natural host. This study examines the local and systemic immune responses of sheep during Fasciola infection and demonstrates that different anatomical tissues display distinct cytokine profiles consistent with Liver Fluke migration. The study also reveals a significant difference in the cytokine and antibody profiles of ITT sheep infected with F. gigantica compared with F. hepatica, with a higher ratio of IL-4/IFN-γ mRNA expression and specific IgG1/IgG2 antibodies strongly correlating with pathology. Interestingly, the significant type-1 cytokine profile occurred in the lymph node closest to the site of infection at a time when the effective immune response against F. gigantica Liver Flukes is thought to occur. When the same F. gigantica infection in the resistant ITT sheep was compared with the susceptible Merino breed, the resistant type-1 phenotype against Liver Fluke infection was only observed in the ITT sheep. These studies provide the first evidence to suggest that the induction of an early type-1 immune response in this natural sheep host may be responsible for the ability to resist Liver Fluke infection.

  • Resistance to Liver Fluke infection in the natural sheep host is correlated with a type‐1 cytokine response
    Parasite immunology, 2011
    Co-Authors: Jill Louise Pleasance, Ening Wiedosari, Herman W. Raadsma, Elza Nicole Theresia Meeusen, David Piedrafita
    Abstract:

    Summary Indonesian thin-tail (ITT) sheep can resist infection with Fasciola gigantica but not F. hepatica and presents an ideal model to investigate the mechanisms of Liver Fluke resistance in a natural host. This study examines the local and systemic immune responses of sheep during Fasciola infection and demonstrates that different anatomical tissues display distinct cytokine profiles consistent with Liver Fluke migration. The study also reveals a significant difference in the cytokine and antibody profiles of ITT sheep infected with F. gigantica compared with F. hepatica, with a higher ratio of IL-4/IFN-γ mRNA expression and specific IgG1/IgG2 antibodies strongly correlating with pathology. Interestingly, the significant type-1 cytokine profile occurred in the lymph node closest to the site of infection at a time when the effective immune response against F. gigantica Liver Flukes is thought to occur. When the same F. gigantica infection in the resistant ITT sheep was compared with the susceptible Merino breed, the resistant type-1 phenotype against Liver Fluke infection was only observed in the ITT sheep. These studies provide the first evidence to suggest that the induction of an early type-1 immune response in this natural sheep host may be responsible for the ability to resist Liver Fluke infection.