Successful intestinal Echinococcus multilocularis oncosphere invasion and subsequent hepatic metacestode establishment in resistant RccHan™:WIST rats after pharmacological immunosuppression

Parasitology ◽  
2016 ◽  
Vol 143 (10) ◽  
pp. 1252-1260 ◽  
Author(s):  
MARIA TERESA ARMUA-FERNANDEZ ◽  
DEBORAH JOEKEL ◽  
ALEXANDER SCHWEIGER ◽  
RAMON MARC EICHENBERGER ◽  
JUN MATSUMOTO ◽  
...  
Keyword(s):  
T Cell ◽  
Host Resistance ◽  
Echinococcus Multilocularis ◽  
Wistar Rats ◽  
Alveolar Echinococcosis ◽  
Parasite Clearance ◽  
Parasite Invasion ◽  
Oral Inoculation ◽  
Complete Resistance ◽  
Successful Establishment

SUMMARYSusceptibility/resistance to larval Echinococcus multilocularis infection varies greatly depending on host species and strains. Whereas several mice strains and non-human primates are highly susceptible to alveolar echinococcosis, rats and most of humans are considered as more resistant. In this study, we aimed to elucidate factors responsible for host resistance in rats (Experiments A–D). (A) The parasite establishment was not observed in immunocompetent Wistar rats orally inoculated with sodium hypochlorite resistant eggs with/without pig bile, or activated/non-activated oncospheres (NAO). Peritoneal inoculation with NAO or metacestode tissue allowed the parasite establishment in rats. (B) T-cell-deficient athymic nude rats showed complete resistance against the metacestode establishment after oral inoculation with parasite eggs. This finding suggests that T-cell-independent parasite clearance occurred in the animals during early phase of the parasite invasion. Finally, Wistar rats that received pharmacological immunosuppression using either dexamethasone (DMS) alone or methotrexate (MTX) i.p. alone or a combination of these compounds were orally inoculated with the parasite's eggs. As a result (D), successful establishment of metacestode with protoscoleces was observed in all 3 rats treated with DMS (s.c.) alone or in all 6 rats treated with DMS (s.c.) plus MTX but not in 8 rats with MTX alone, suggesting that factors affected by DMS treatment are responsible to regulate the parasite invasion and establishment.

scholarly journals Agranulocytosis leads to intestinal Echinococcus multilocularis oncosphere invasion and hepatic metacestode development in naturally resistant Wistar rats

Parasitology ◽  
2020 ◽  
pp. 1-10
Author(s):  
Deborah E. Joekel ◽  
Selim Nur ◽  
Josep Monné Rodriguez ◽  
Philipp A. Kronenberg ◽  
Anja Kipar ◽  
...  
Keyword(s):  
Echinococcus Multilocularis ◽  
Wistar Rats ◽  
Nk Cell ◽  
Immunosuppressive Treatment ◽  
Polymorphonuclear Cells ◽  
Resistant Species ◽  
Dead End ◽  
Oral Inoculation ◽  
Neutrophil Response

Abstract Susceptibility to Echinococcus multilocularis infection considerably varies among intermediate (mostly rodents) and dead-end host species (e.g. humans and pig), in particular regarding intestinal oncosphere invasion and subsequent hepatic metacestode development. Wistar rats are highly resistant to infection and subsequent diseases upon oral inoculation with E. multilocularis eggs, however, after immunosuppressive treatment with dexamethasone, rats become susceptible. To address the role of the cellular innate immunity, Wistar rats were individually or combined depleted of natural killer (NK) cells, macrophages (MΦ) and granulocytes (polymorphonuclear cells, PMN) prior to E. multilocularis egg inoculation. Although NK cell and MΦ depletion did not alter the resistance status of rats, the majority of PMN-depleted animals developed liver metacestodes within 10 weeks, indicating that PMN are key players in preventing oncosphere migration and/or development in Wistar rats. In vitro studies indicated that resistance is not caused by neutrophil reactive oxygen species or NETosis. Also, light microscopical examinations of the small intestine showed that oral inoculation of E. multilocularis eggs does not elicit a mucosal neutrophil response, suggesting that the interaction of oncospheres and neutrophils may occur after the former have entered the peripheral blood. We suggest to consider granulocytes as mediators of resistance in more resistant species, such as humans.

Surgical treatment of alveolar echinococcosis: a single centre experience and systematic review of the literature

2019 ◽  
Vol 98 (4) ◽  
pp. 167-173
Keyword(s):  
Case Report ◽  
Echinococcus Multilocularis ◽  
Alveolar Echinococcosis ◽  
Lymphatic System ◽  
Surgical Intervention ◽  
Clinical Symptoms ◽  
Safety Margin ◽  
Surgical Removal ◽  
Single Centre Experience ◽  
Therapeutic Procedures

Introduction: Alveolar echinococcosis (AE) is a zoonosis caused by Echinococcus multilocularis. AE is primarily localised in the liver. Echinococcus multilocularis imitates tumour-like behaviour. It can metastasise through blood or lymphatic system to distant organs. Echinococcosis often remains asymptomatic due to its long incubation period and indistinct symptoms. Clinical symptoms are determined by the parasite’s location. Diagnosis of echinococcosis is based on medical history, clinical symptoms, laboratory tests, serology results, imaging methods and final histology findings. Surgical removal of the cyst with a safety margin, followed by chemotherapy is the therapeutic method of choice. Case report: We present a case report of alveolar echinococcosis in a thirty-year-old female patient in whom we surgically removed multiple liver foci of alveolar echinococcosis. The disease recurred after two years and required another surgical intervention. Conclusions: Alveolar echinococcosis is a disease with a high potential for a complete cure provided that it is diagnosed early and that the recommended therapeutic procedures are strictly adhered to.

scholarly journals Batf3-Dependent Dendritic Cells Promote Optimal CD8 T Cell Responses against Respiratory Poxvirus Infection

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Pritesh Desai ◽  
Vikas Tahiliani ◽  
Georges Abboud ◽  
Jessica Stanfield ◽  
Shahram Salek-Ardakani
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Vaccinia Virus ◽  
Respiratory Infection ◽  
Host Resistance ◽  
T Cell Responses ◽  
Cell Responses ◽  
Ifn Γ ◽  
The Impact

ABSTRACTRespiratory infection with vaccinia virus (VacV) elicits robust CD8+T cell responses that play an important role in host resistance. In the lung, VacV encounters multiple tissue-resident antigen-presenting cell (APC) populations, but which cell plays a dominant role in priming of virus-specific CD8+effector T cell responses remains poorly defined. We used Batf3−/−mice to investigate the impact of CD103+and CD8α+dendritic cell (DC) deficiency on anti-VacV CD8+T cell responses. We found that Batf3−/−mice were more susceptible to VacV infection, exhibiting profound weight loss, which correlated with impaired accumulation of gamma interferon (IFN-γ)-producing CD8+T cells in the lungs. This was largely due to defective priming since early in the response, antigen-specific CD8+T cells in the draining lymph nodes of Batf3−/−mice expressed significantly reduced levels of Ki67, CD25, and T-bet. These results underscore a specific role for Batf3-dependent DCs in regulating priming and expansion of effector CD8+T cells necessary for host resistance against acute respiratory VacV infection.IMPORTANCEDuring respiratory infection with vaccinia virus (VacV), a member ofPoxviridaefamily, CD8+T cells play important role in resolving the primary infection. Effector CD8+T cells clear the virus by accumulating in the infected lungs in large numbers and secreting molecules such as IFN-γ that kill virally infected cells. However, precise cell types that regulate the generation of effector CD8+T cells in the lungs are not well defined. Dendritic cells (DCs) are a heterogeneous population of immune cells that are recognized as key initiators and regulators of T-cell-mediated immunity. In this study, we reveal that a specific subset of DCs that are dependent on the transcription factor Batf3 for their development regulate the magnitude of CD8+T cell effector responses in the lungs, thereby providing protection during pulmonary VacV infection.

scholarly journals Echinococcus spp.: Tapeworms that Pose a Danger to Both Animals and Humans – a Review

2017 ◽  
Vol 48 (4) ◽  
pp. 193-201 ◽  
Author(s):  
A. Brožová ◽  
I. Jankovská ◽  
V. Bejček ◽  
S. Nechybová ◽  
P. Peřinková ◽  
...  
Keyword(s):  
Small Intestine ◽  
Life Cycle ◽  
Echinococcus Multilocularis ◽  
Alveolar Echinococcosis ◽  
Sensu Stricto ◽  
Mammal Species ◽  
Current State ◽  
Wide Range ◽  
The World ◽  
Echinococcus Spp

Abstract Species of the genus Echinococcus (Cestoda; Taeniidae) are minute tapeworms of carnivores. Their larvae are known as hydatids (metacestode), which proliferate asexually in various mammals. Like the majority of cestodes, Echinococcus spp. require two different host species to complete their life cycle. Definitive hosts harbouring the adult cestodes in the small intestine are exclusively carnivores of the Canidae and Felidae families. A wide range of mammal species including humans is susceptible to infection by the metacestode of Echinococcus spp., which develops in their viscera. The disease, caused by species of the genus Echinococcus, is called echinococcosis, and it is one of the most dangerous zoonoses in the world. The traditional species Echinococcus granulosus and Echinococcus multilocularis are agents of significant diseases due to the high number of cases and the wide geographical species range. The taxonomy of the genus is controversial; in the current state of ongoing complex revisions, the agent of cystic echinococcosis E. granulosus sensu lato is divided into five species (E. granulosus sensu stricto, E. felidis, E. equinus, E. ortleppi, E. canadensis), in addition to the agents of alveolar echinococcosis (E. multilocularis, E. shiquicus) and polycystic/unicystic echinococcosis (E. vogeli, E. oligarthrus). Here we provide an overview of the current situation, which continues to develop.

scholarly journals Albendazole reduces endoplasmic reticulum stress induced by Echinococcus multilocularis in mice

2021 ◽  
Author(s):  
Michael Weingartner ◽  
Fadi Jebbawi ◽  
Junhua Wang ◽  
Simon Stücheli ◽  
Bruno Gottstein ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protein Expression ◽  
Echinococcus Multilocularis ◽  
Liver Tissue ◽  
Alveolar Echinococcosis ◽  
Surgical Intervention ◽  
Fatal Disease ◽  
Unfolded Protein ◽  
Protein Response

AbstractBackgroundEchinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with relatively frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice.MethodsE. multilocularis- and mock-infected C57BL/6 mice were subdivided six weeks after infection into vehicle and albendazole (ABZ) treated groups. Eight weeks later, liver tissue was collected to examine mRNA, microRNA (miR) and protein expression of UPR- and ERS-related genes.ResultsE. multilocularis infection upregulated UPR- and ERS-related proteins, including ATF6, CHOP, GRP78, ERP72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed the increased ATF6 and calreticulin protein expression, tended to reverse increased CHOP, GRP78, ERP72 and H6PD expression, and decreased ATF4 and IRE1α expression to levels seen in mock-infected mice. The expression of miR-146a-5p (downregulated by IRE1α) and miR-1839-5p (exhibiting a unique target site in the IRE1α 3’UTR) were significantly increased in E. multilocularis infected mice, an effect reversed by ABZ treatment. Other miRs analyzed were not altered in E. multilocularis infected mice.Conclusions and SignificanceAE causes UPR activation and ERS in mice. The E. multilocularis-induced ERS was ameliorated by ABZ treatment, indicating its effectiveness to inhibit parasite proliferation and downregulate its activity status. ABZ itself did not affect UPR in control mice. Identified miR-146a-5p and miR-1839-5p might represent biomarkers of E. multilocularis infection. Modulation of UPR and ERS, in addition to ABZ administration, could be exploited to treat E. multilocularis infection.Author summaryAlveolar echinococcosis is a zoonotic disease caused by the fox tapeworm Echinococcus multilocularis. Treatment of this fatal disease is limited to surgical intervention, preferably radical curative surgery if possible, and the use of parasitostatic benzimidazoles. It is not yet fully understood how the parasite can remain in the host’s tissue for prolonged periods, complicating the development of therapeutic applications. This work investigated an involvement of the unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection and upon treatment with albendazole (ABZ) in mice. The results revealed increased expression levels of the ERS sensor ATF6 and of downstream target genes in liver tissue of E. multilocularis- compared to mock-infected mice. Additionally, H6PD, generating NADPH within the endoplasmic reticulum, and the lectin-chaperone calreticulin were increased in E. multilocularis infected liver tissue while the expression of the ERS associated genes ATF4 and IRE1α were decreased. The miR-1839-5p and miR-146-p, linked to IRE1α, were elevated upon E. multilocularis infection, offering potential as novel biomarkers of alveolar echinococcosis. The observed gene expression changes were at least partially reversed by ABZ treatment. Whether modulation of UPR and ERS targets can improve the therapy of alveolar echinococcosis remains to be investigated.

scholarly journals The expression of nuclear factor of activated T cell c1 and receptor activator of nuclear factor kappa β induced by Enterococcus faecalis in osteoclastogenesis (laboratory experiment on Wistar rats)

2019 ◽  
Vol 52 (4) ◽  
pp. 172
Author(s):  
Nirawati Pribadi ◽  
Rosita Rahmawati ◽  
Mandojo Rukmo ◽  
Adelina Kristanti Tandadjaja ◽  
Hendy Jaya Kurniawan ◽  
...  
Keyword(s):  
T Cell ◽  
Enterococcus Faecalis ◽  
Wistar Rats ◽  
Bone Defects ◽  
Control Group ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Endodontic Infection ◽  
Receptor Activator ◽  
Activated T Cell

Background: Enterococcus faecalis (E. faecalis) is the most common bacteria species in persistent endodontic infection of teeth undergoing root canal treatment at a prevalence of 38%. The virulence factor of this bacterium is Lipoteichoic acid (LTA) which can be recognized by Toll-like receptors-4 (TLR-4) that produce a stimulus and provoke an immune response. Inflammation results in bone defects that feature multiple cytokines and interactions between different cell types. Bone loss within a periapical tooth is characterized by osteoclast formation (osteoclastogenesis) in the bone. Purpose: This study aimed to determine the expression of nuclear factor of activated T cell c1 (NFATc1) and receptor activator of nuclear factor kappa β (RANK) which played a role in osteoclastogenesis at different time intervals. Methods: 36 upper molar teeth of the research subjects were induced with 106 CFU Enterococcus faecalis and subsequently observed for 7 and 21 days with the NFATc1 and RANK being counted microscopically at 1000X magnification across 20 viewing fields. Thereafter, the data was examined and analyzed by means of an independent T test using SPSS. Results: NFATc1 and RANK expression were higher in the group including E. faecalis on days 7 and 21 than in the control group. There were significant differences between the treatment group and control group with regard to NFATc1 and RANK expression (p<0.05). Conclusion: The study showed that the expression of NFATc1 and RANK, which plays a role in osteoclastogenesis, was higher in periapical bone defects in Wistar rats induced by E. faecalis than those which were not induced.

scholarly journals T-Cell Production of Matrix Metalloproteinases and Inhibition of Parasite Clearance by TIMP-1 During ChronicToxoplasmaInfection in the Brain

ASN NEURO ◽  
2010 ◽  
Vol 3 (1) ◽  
pp. AN20100027 ◽  
Author(s):  
Robin T Clark ◽  
J Philip Nance ◽  
Shahani Noor ◽  
Emma H Wilson
Keyword(s):  
T Cell ◽  
Matrix Metalloproteinases ◽  
Parasite Clearance ◽  
Cell Production ◽  
The Brain

Hepatic Alveolar Echinococcosis

2021 ◽  
Author(s):  
Solange Bresson-Hadni ◽  
Laurent Spahr ◽  
François Chappuis
Keyword(s):  
Access To Care ◽  
Surgical Resection ◽  
Larval Stage ◽  
Echinococcus Multilocularis ◽  
Gold Standard ◽  
Diagnostic Procedure ◽  
Alveolar Echinococcosis ◽  
Opportunistic Infections ◽  
First Line ◽  
Hepatic Alveolar Echinococcosis

AbstractHepatic alveolar echinococcosis (HAE) is a rare but severe zoonosis caused by the pseudotumoral intrahepatic development of the larval stage of the tapeworm Echinococcus multilocularis. HAE is present only in the Northern Hemisphere, predominantly in China. Currently, there is a significant resurgence of cases in historically endemic areas associated with emergence of HAE in countries not previously concerned. Today, in European countries, HAE is often discovered by chance; however, clinicians should be made aware of opportunistic infections that progressively emerged recently as a result of therapeutic or pathological immunosuppression. Ultrasonography is the key first-line diagnostic procedure, with specific serology providing confirmation in 95% of the cases. Albendazole, only parasitostatic, is the mainstay for treatment. Surgical resection, if feasible, is the gold standard for treatment, and more patients are currently eligible for this option because of an earlier diagnosis. The prognosis has considerably improved but remains poor in countries where access to care is less favorable.

scholarly journals Alveolar Echinococcosis in Children

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Emilija Jonaitytė ◽  
Martynas Judickas ◽  
Eglė Tamulevičienė ◽  
Milda Šeškutė
Keyword(s):  
Surgical Treatment ◽  
Current Literature ◽  
Echinococcus Multilocularis ◽  
Cystic Echinococcosis ◽  
Alveolar Echinococcosis ◽  
Pediatric Patients ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Diagnostic Methods

Alveolar echinococcosis (AE) is an infectious zoonotic disease that is caused by Echinococcus multilocularis. The disease is generally identified accidentally because of the long asymptomatic period, has a malignant behaviour, and mainly occurs in the liver. Usually it is diagnosed in adults and is very rare in pediatric patients. We report two cases of AE and 1 differential case between AE and cystic echinococcosis (CE) in children: two of them had lesions in the liver and one had rare extrahepatic presentation of a cyst in the spleen. All our patients received chemotherapy with albendazole because surgical treatment was not recommended. The children were followed-up from 10 to 30 months and no significant improvement was seen. In this report we discuss the difficulties we faced in the treatment and follow-up of these patients. We also review the main clinical manifestations, general diagnostic methods, and treatment options of AE according to the current literature.

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