Trends in Parasitology
ReviewInsights into Fasciola hepatica Juveniles: Crossing the Fasciolosis Rubicon
Section snippets
Studies on Fasciola hepatica: The Adult Worm Is the Leading Actor (to Date)
Fasciolosis is a foodborne zoonotic disease (see Glossary) caused by trematodes of the genus Fasciola, of which F. hepatica is the most geographically widespread species [1]. Also known as the liver fluke, F. hepatica is maintained in an indirect life cycle with an invertebrate host (snails) and a vertebrate host (mainly large-size herbivorous species commonly raised as livestock) (Figure 1). Animal morbidity and mortality due to fasciolosis is of importance for stockbreeding worldwide in
F. hepatica Juvenile Biology: The Parasite Tegument as a Key Point to Unravel Host–Parasite Interactions in Fasciolosis
FhNEJ penetrate the gut wall of their vertebrate host, shortly after excystment, in order to enter the body cavity, and then the parasites crawl up the peritoneum until they reach the liver. There, the juvenile liver flukes spend several weeks burrowing through (and feeding on) the liver parenchyma, causing acute fasciolosis, eventually reaching the bile ducts. During these early events, F. hepatica intimately interacts with the host, mainly through the components of its tegument, which
The Metabolism of F. hepatica Juveniles: The Path towards an Anaerobic Environment
The transformation of FhNEJ into juvenile liver flukes and later into adult worms, occurring in changing environments, results in drastic metabolic changes during parasite migration and development inside their vertebrate host. Glucose catabolism is the best described metabolic difference between FhNEJ and the adult worm. Adult flukes are fully anaerobic, and the main product of glucose cytosolic degradation at this stage is acetate, while FhNEJ mainly use the aerobic route when freshly
Crossing the Intestinal Wall of the Host, the 'Point of No Return' in Fasciolosis: Locomotion and Migration
Parasite migration, breaking through host tissues before reaching maturity, is common to several helminth parasites. In spite of being a process with high energy and adaptive costs for the parasite, the conservation of migration routes in many helminth parasites suggests that this process confers evolutionary benefits in terms of parasite fitness [32]. In addition, parasite migration has been proposed as a potential mechanism of immune evasion that arose due to the evolution of T helper 2 (Th2)
FhNEJ as Therapeutic Targets: Success or Failure?
Worldwide, annual losses associated with fasciolosis due to the parasite's impact on farm profitability have been estimated at around 3 billion US dollars [63]. Therefore, there is a clear need to develop effective tools to control animal fasciolosis, not only in response to the current demands on sustainable food production but also because of the relationship between high prevalence in livestock and epidemiology in humans. Currently, human fasciolosis affects at least 2.4 million people in
-Omics Technologies of the New Era: Genomic, Transcriptomic, and Proteomic Approaches
-Omics datasets are a powerful resource that are potentially useful for the identification of new therapeutic targets against fasciolosis [82]. -Omics studies on fasciolosis were substantially enhanced after the publication of the first F. hepatica genome draft by Cwiklinski et al. [53], as well as with the subsequent parasite genome assemblies [45,83] which revealed some interesting features, such as the unusually large size of the F. hepatica genome and its high degree of polymorphism [53].
Concluding Remarks
F. hepatica flukes reach their definitive location in the host after a complex migratory route leading the parasites to the bile ducts from the small intestine. There, they become sexually mature and start shedding eggs in a process that can last for more than 10 years. The chronicity of the infection relies not only on the fine immunomodulatory mechanisms developed by the adult flukes but also on the fact that the biliary tract constitutes a niche that is poorly accessible to the host immune
Acknowledgments
J.G.M. is supported by the 'Juan de la Cierva-Incorporación' program (IJC2018-036660-I) of the Ministerio de Ciencia, Innovación y Universidades (MCIU) and by the JIN project 'ULYSSES' (RTI2018-093463-J-100) funded by MCIU, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, UE). D.B.R. is supported by a predoctoral fellowship from Junta de Castilla y León and the European Social Fund. Authors acknowledge financial support from MCIU (Projects
Glossary
- Fluke
- common name given to parasitic flatworms of the class Trematoda (phylum Platyhelminthes). More than 6000 species are included within this class. Adult stages range in size from about 5 mm to several cm. They are flattened and leaflike or ribbonlike with muscular suckers on the ventral surface that are employed to anchor themselves within their host.
- Foodborne zoonotic disease
- any disease or infection which is transmitted from vertebrate animals to humans by food consumption. These diseases
References (98)
A review on epidemiology, global prevalence and economical losses of fasciolosis in ruminants
Microb. Pathog.
(2017)Fascioliasis and other plant-borne trematode zoonoses
Int. J. Parasitol.
(2005)Current threat of triclabendazole resistance in Fasciola hepatica
Trends Parasitol.
(2016)Reducing the future threat from (liver) fluke: realistic prospect or quixotic fantasy?
Vet. Parasitol.
(2011)Immunomodulatory molecules of Fasciola hepatica: candidates for both vaccine and immunotherapeutic development
Vet. Parasitol.
(2013)Low allelic diversity in vaccine candidates genes from different locations sustain hope for Fasciola hepatica immunization
Vet. Parasitol.
(2018)Fasciola hepatica: an antigen fraction derived from newly excysted juveniles, containing an immunoreactive 32-kDa protein, induces strong protective immunity in rats
Exp. Parasitol.
(2000)- et al.
Evidence for two distinct mechanisms of resistance in the rat to reinfection with Fasciola hepatica
Int. J. Parasitol.
(1982) - et al.
Resistance to fascioliasis – a review
Vet. Parasitol.
(1986) Exploring the Fasciola hepatica tegument proteome
Int. J. Parasitol.
(2011)
Fasciola hepatica surface tegument: glycoproteins at the interface of parasite and host
Mol. Cell. Proteom.
Fasciola hepatica: development of tegument during migration in mouse
Exp. Parasitol.
The shedding of the outer glycocalyx of juvenile Fasciola hepatica
Vet. Parasitol.
Fasciola hepatica: glycocalyx replacement in the juvenile as a possible mechanism for protection against host immunity
Exp. Parasitol.
The ultrastructure of the 'cuticle' of Fasciola hepatica
Exp. Cell Res.
Fasciola hepatica: an immunofluorescent study of antigenic changes in the tegument during development in the rat and the sheep
Exp. Parasitol.
Fasciola gigantica: Comparison of the tegumental ultrastructure in newly excysted metacercariae and in vitro penetrated juvenile flukes indicates intracellular sources of molecules with vaccinal and immunomodulatory potential
Vet. Parasitol.
The extracellular vesicles of the helminth pathogen, Fasciola hepatica: biogenesis pathways and cargo molecules involved in parasite pathogenesis
Mol. Cell. Proteom.
Changes in energy metabolism of the juvenile Fasciola hepatica during its development in the liver parenchyma
Mol. Biochem. Parasitol.
The aerobic energy metabolism of the juvenile Fasciola hepatica
Mol. Biochem. Parasitol.
Differences in intermediary energy metabolism between juvenile and adult Fasciola hepatica
Mol. Biochem. Parasitol.
The energy metabolism of Fasciola hepatica during its development in the final host
Mol. Biochem. Parasitol.
Infection by the helminth parasite Fasciola hepatica requires rapid regulation of metabolic, virulence, and invasive factors to adjust to its mammalian host
Mol. Cell. Proteom.
Tissue migration by parasitic helminths – an immunoevasive strategy?
Trends Parasitol.
Controversial aspects of the life cycle of Fasciola hepatica
Exp. Parasitol.
Fasciola hepatica: simple, large-scale, in vitro excystment of metacercariae and subsequent isolation of juvenile liver flukes
Exp. Parasitol.
A novel ex vivo rat infection model to study protective immunity against Fasciola hepatica at the gut level
J. Immunol. Methods
Trichostrongylus colubriformis induces IgE-independent CD13, CD164 and CD203c mediated activation of basophils in an in vitro intestinal epithelial cell co-culture model
Vet. Parasitol.
Set up of an in vitro model to study early host–parasite interactions between newly excysted juveniles of Fasciola hepatica and host intestinal cells using a quantitative proteomics approach
Vet. Parasitol.
The cathepsin-like cysteine peptidases of trematodes of the genus Fasciola
Adv. Parasitol.
Proteomics and phylogenetic analysis of the cathepsin L protease family of the helminth pathogen Fasciola hepatica: expansion of a repertoire of virulence-associated factors
Mol. Cell. Proteom.
An integrated transcriptomics and proteomics analysis of the secretome of the helminth pathogen Fasciola hepatica: proteins associated with invasion and infection of the mammalian host
Mol. Cell. Proteom.
A major cathepsin B protease from the liver fluke Fasciola hepatica has atypical active site features and a potential role in the digestive tract of newly excysted juvenile parasites
Int. J. Biochem. Cell Biol.
The major cathepsin L secreted by the invasive juvenile Fasciola hepatica prefers proline in the S2 subsite and can cleave collagen
Mol. Biochem. Parasitol.
Fasciola hepatica virulence-associated cysteine peptidases: a systems biology perspective
Microbes Infect.
The silencing of cysteine proteases in Fasciola hepatica newly excysted juveniles using RNA interference reduces gut penetration
Int. J. Parasitol.
Plasmin in parasitic chronic infections: friend or foe?
Trends Parasitol.
Techniques for the diagnosis of Fasciola infections in animals: room for improvement
Adv. Parasitol.
Understanding triclabendazole resistance
Exp. Mol. Pathol.
Drug resistance in liver flukes
Int. J. Parasitol. Drugs Drug Resist.
Tegumental surface changes in juvenile Fasciola hepatica in response to treatment in vivo with triclabendazole
Vet. Parasitol.
Liver fluke vaccines in ruminants: strategies, progress and future opportunities
Int. J. Parasitol.
Fasciola hepatica vaccine: we may not be there yet but we're on the right road
Vet. Parasitol.
Fasciola hepatica: migration of newly excysted juveniles in resistant rats
Exp. Parasitol.
A novel ex vivo immunoproteomic approach characterising Fasciola hepatica tegumental antigens identified using immune antibody from resistant sheep
Int. J. Parasitol.
Fasciola hepatica procathepsin L3 protein expressed by a baculovirus recombinant can partly protect rats against fasciolosis
Vaccine
Vaccination against fasciolosis by a multivalent vaccine of stage-specific antigens
Vet. Parasitol.
Antibody recognition of cathepsin L1-derived peptides in Fasciola hepatica-infected and/or vaccinated cattle and identification of protective linear B-cell epitopes
Vaccine
Sex and vaccination: Insights from female rats vaccinated with juvenile-specific proteases from Fasciola hepatica
Vet. Parasitol.
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In vitro and in vivo studies on a group of chalcones find promising results as potential drugs against fascioliasis
2023, Experimental ParasitologyGlycan complexity and heterogeneity of glycoproteins in somatic extracts and secretome of the infective stage of the helminth fasciola hepatica
2023, Molecular and Cellular ProteomicsOmics tools enabling vaccine discovery against fasciolosis
2022, Trends in ParasitologyCitation Excerpt :Nevertheless, it may signal that more antigens in vaccine cocktails is not necessarily better than individual antigens, and it raises doubts concerning which combination of antigens should be used and how we assess the contribution of each individual antigen in vaccine efficacy versus their amalgamated effect. Recent vaccine strategies are aimed at preventing the damaging effects of the parasite’s invasion and migration through the liver tissues rather than focussing on molecules released by the adult parasites that represent long-established infections [62,64]. Moreover, once in the liver, the rapid growth, development, and continuous movement of the parasite makes the immune response of the host rather ineffectual as the parasite has moved on (with the exception of the immune responses observed in F. gigantica-infected ITT sheep).
Antigens from the Helminth Fasciola hepatica Exert Antiviral Effects against SARS-CoV-2 In Vitro
2023, International Journal of Molecular Sciences