Trends in Parasitology
Volume 37, Issue 1, January 2021, Pages 35-47
Journal home page for Trends in Parasitology

Review
Insights into Fasciola hepatica Juveniles: Crossing the Fasciolosis Rubicon

https://doi.org/10.1016/j.pt.2020.09.007Get rights and content

Highlights

  • Control strategies against fasciolosis have been generally directed towards the adult form of the parasite, even though its definitive location in the host bile ducts represents a niche that seems to be poorly accessible to the host immunity.

  • Despite its importance during the course of infection, research studies aimed at unraveling host–parasite crosstalk at the early stages of fasciolosis are still scarce.

  • We review the most recent available data on the Fasciola hepatica juveniles in relation to their biology, metabolism, and antigenic repertoire, their key functions in parasite migration and immune evasion, and their potential as therapeutic targets.

  • We highlight the latest developments in in vitro models to study the host–juvenile parasite interface, and the potential of new -omics approaches as tools for identifying effective therapeutic strategies against fasciolosis.

Unraveling the molecular interactions governing the first contact between parasite and host tissues is of paramount importance to the development of effective control strategies against parasites. In fasciolosis, a foodborne trematodiasis caused mainly by Fasciola hepatica, these early interactions occur between the juvenile worm and the host intestinal wall a few hours after ingestion of metacercariae, the infectious stage of the parasite. However, research on these early events is still scarce and the majority of studies have focused on the adult worm. Here, we review current knowledge on the biology and biochemistry of F. hepatica juveniles and their molecular relationships with the host tissues and identify the research needs and gaps to be covered in the future.

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

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