Relationship between hepatic grayish-white solid nodules in horses imported from Canada and larval Echinococcus multilocularis infection.
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ABSTRACT:
SUBMITTER: Hifumi T
PROVIDER: S-EPMC7877675 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSerotonin is a phylogenetically ancient molecule that is widely distributed in most metazoans, including flatworms. In addition to its role as a neurotransmitter, serotonin acts as a morphogen and regulates developmental processes. Although several studies have focused on the serotonergic nervous system in parasitic flatworms, little is known on the role of serotonin in flatworm development.MethodsTo study the effects of serotonin on proliferation and development of the cestode Echinococcus multilocularis, we cloned the genes encoding the E. multilocularis serotonin transporter (SERT) and tryptophan hydroxylase (TPH), analyzed gene expression by transcriptome analysis and whole mount in situ hybridization (WMISH) and performed cell culture experiments.ResultsWe first characterized orthologues encoding the SERT and TPH, the rate-limiting enzyme in serotonin biosynthesis. WMISH and transcriptomic analyses indicated that the genes for both SERT and TPH are expressed in the parasite nervous system. Long-term treatment of parasite stem cell cultures with serotonin stimulated development towards the parasite metacestode stage. Mature metacestode vesicles treated with serotonin showed increased rates of incorporation of the thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU), indicating stimulated cell proliferation. In contrast, treatment with the selective serotonin reuptake inhibitor paroxetine strongly affected the viability of parasite cells. Paroxetine also caused structural damage in metacestode vesicles, suggesting that serotonin transport is crucial for the integrity of parasite vesicles.ConclusionsOur results indicate that serotonin plays an important role in E. multilocularis development and proliferation, providing evidence that the E. multilocularis SERT and TPH are expressed in the nervous system of the protoscolex. Our results further suggest that the E. multilocularis SERT has a secondary role outside the nervous system that is essential for parasite integrity and survival. Since serotonin stimulated E. multilocularis metacestode development and proliferation, serotonin might also contribute to the formation and growth of the parasite in the liver.
| S-EPMC7789706 | biostudies-literature
Project description:BackgroundThe metacestode larva of Echinococcus multilocularis (Cestoda: Taeniidae) develops in the liver of intermediate hosts (typically rodents, or accidentally in humans) as a labyrinth of interconnected cysts that infiltrate the host tissue, causing the disease alveolar echinococcosis. Within the cysts, protoscoleces (the infective stage for the definitive canid host) arise by asexual multiplication. These consist of a scolex similar to that of the adult, invaginated within a small posterior body. Despite the importance of alveolar echinococcosis for human health, relatively little is known about the basic biology, anatomy and development of E. multilocularis larvae, particularly with regard to their nervous system.ResultsWe describe the existence of a subtegumental nerve net in the metacestode cysts, which is immunoreactive for acetylated tubulin-α and contains small populations of nerve cells that are labeled by antibodies raised against several invertebrate neuropeptides. However, no evidence was found for the existence of cholinergic or serotoninergic elements in the cyst wall. Muscle fibers occur without any specific arrangement in the subtegumental layer, and accumulate during the invaginations of the cyst wall that form brood capsules, where protoscoleces develop. The nervous system of the protoscolex develops independently of that of the metacestode cyst, with an antero-posterior developmental gradient. The combination of antibodies against several nervous system markers resulted in a detailed description of the protoscolex nervous system, which is remarkably complex and already similar to that of the adult worm.ConclusionsWe provide evidence for the first time of the existence of a nervous system in the metacestode cyst wall, which is remarkable given the lack of motility of this larval stage, and the lack of serotoninergic and cholinergic elements. We propose that it could function as a neuroendocrine system, derived from the nervous system present in the bladder tissue of other taeniids. The detailed description of the development and anatomy of the protoscolex neuromuscular system is a necessary first step toward the understanding of the developmental mechanisms operating in these peculiar larval stages.
| S-EPMC3658878 | biostudies-literature
Project description:BackgroundThe metacestode of the tapeworm Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a lethal zoonosis. Infections are initiated through establishment of parasite larvae within the intermediate host's liver, where high concentrations of insulin are present, followed by tumour-like growth of the metacestode in host organs. The molecular mechanisms determining the organ tropism of E. multilocularis or the influences of host hormones on parasite proliferation are poorly understood.ResultsUsing in vitro cultivation systems for parasite larvae we show that physiological concentrations (10 nM) of human insulin significantly stimulate the formation of metacestode larvae from parasite stem cells and promote asexual growth of the metacestode. Addition of human insulin to parasite larvae led to increased glucose uptake and enhanced phosphorylation of Echinococcus insulin signalling components, including an insulin receptor-like kinase, EmIR1, for which we demonstrate predominant expression in the parasite's glycogen storage cells. We also characterized a second insulin receptor family member, EmIR2, and demonstrated interaction of its ligand binding domain with human insulin in the yeast two-hybrid system. Addition of an insulin receptor inhibitor resulted in metacestode killing, prevented metacestode development from parasite stem cells, and impaired the activation of insulin signalling pathways through host insulin.ConclusionsOur data indicate that host insulin acts as a stimulant for parasite development within the host liver and that E. multilocularis senses the host hormone through an evolutionarily conserved insulin signalling pathway. Hormonal host-parasite cross-communication, facilitated by the relatively close phylogenetic relationship between E. multilocularis and its mammalian hosts, thus appears to be important in the pathology of alveolar echinococcosis. This contributes to a closer understanding of organ tropism and parasite persistence in larval cestode infections. Furthermore, our data show that Echinococcus insulin signalling pathways are promising targets for the development of novel drugs.
| S-EPMC3923246 | biostudies-literature
Project description:An immunocompetent child in Canada received a diagnosis of disseminated alveolar Echinococcus multilocularis infection. The case lacked typical features of liver involvement and was possibly related to a rare congenital portosystemic shunt. We summarize the rapidly evolving epidemiology of E. multilocularis parasites in Canada.
| S-EPMC7392456 | biostudies-literature
Project description:Echinococcus multilocularis is a zoonotic cestode with a distribution encompassing the northern hemisphere that causes alveolar hydatid disease in people and other aberrant hosts. E. multilocularis is not genetically uniform across its distribution, which may have implications for zoonotic transmission and pathogenicity. Recent findings of a European-type haplotype of E. multilocularis in wildlife in one location in western Canada motivated a broader survey of the diversity of this parasite in wildlife from northern and western Canada. We obtained intact adult cestodes of E. multilocularis from the intestines of 41 wild canids (wolf - Canis lupus, coyote - Canis latrans, and red fox - Vulpes vulpes), taeniid eggs from 28 fecal samples from Arctic fox (Vulpes lagopus), and alveolar hydatid cysts from 39 potential rodent intermediate hosts. Upon sequencing a 370-nucelotide region of the NADH dehydrogenase subunit 1 (nad1) mitochondrial locus, 17 new haplotypes were identified. This constitutes a much higher diversity than expected, as only two genotypes (European and an Asian/North American) had previously been identified using this locus. The European-type strain, recently introduced, may be widespread in wildlife within western Canada, possibly related to the large home ranges and wide dispersal range of wild canids. This study increased understanding of the biogeographic distribution, prevalence and genetic differences of a globally important pathogenic cestode in northern and western Canada.
| S-EPMC4142260 | biostudies-literature
Project description:Hepatocyte-based metacestode culture is an attractive method to study alveolar echinococcosis (AE), but it is limited by the relatively short lifespan of cultured hepatocytes in maintaining their normal function.We describe a three-dimensional (3D) hepatic culture system developed from co-cultured hepatocytes and mesenchymal stem cells using a collagen scaffold to study the development of Echinococcus multilocularis larvae. This 3D culture system preserved the function of hepatocytes for a longer period of time than their monolayer counterparts, with albumin secretion, 7-ethoxyresorufin O-deethylation activity, urea synthesis, CYP3A4 and CYP2D6 activity being highly preserved for 21-28 days. The expression levels of hepatocyte-specific genes including CLDN-3, Bsep, AFP, G6P, A1AT, CYP3A4 and NR1I3 were significantly higher in the 3D cultured system compared with their monolayer counterparts after 14-days in culture. Additionally, in the presence of 3D cultured hepatocytes, 81.2% of E. multilocularis protoscoleces rapidly de-differentiated into infective vesicles within eight weeks. Transcriptomic analyses revealed 807 differentially expressed genes between cultured vesicles and protoscoleces, including 119 genes uniquely expressed in protoscoleces, and 242 genes uniquely expressed in vesicles. These differentially expressed genes were mainly involved in parasite growth relating to the G-protein coupled receptor activity pathway, substrate-specific transmembrane transporter activity, cell-cell adhesion process, and potentially with neuroactive ligand-receptor interaction.This culture system provides a valuable advance in prolonging hepatocyte functionality, a foundation for future in-depth analysis of the host-parasite interaction in AE, and a useful model to evaluate potential therapeutic strategies to treat AE.
| S-EPMC5868855 | biostudies-literature
Project description:Transcriptome profile changes during the early larval development from egg of Echinococcus multilocularis
| PRJDB3524 | ENA
Project description:Echinococcus multilocularis Variation
| PRJNA388637 | ENA
Project description:Echinococcus multilocularis RefSeq Genome
| PRJNA308738 | ENA
Project description:Echinococcus multilocularis overview
| PRJNA213891 | ENA