myo-Inositol hexakisphosphate is a major component of an extracellular structure in the parasitic cestode Echinococcus granulosus

myo-Inositol hexakisphosphate (IP6) is an abundant intracellular component of animal cells. In this study we describe the presence of extracellular IP6 in the hydatid cyst wall (HCW) of the larval stage of the cestode parasite Echinococcus granulosus. The HCW comprises an inner cellular layer and an outer, acellular (laminated) layer up to 2mm in thickness that protects the parasite from host immune cells. A compound, subsequently identified as IP6, was detected in and purified from an HCW extract on the basis of its capacity to inhibit complement activation. The identification of the isolated compound was carried out by a combination of NMR, MS and TLC. The majority of IP6 in the HCW was found in the acellular layer, with only a small fraction of the compound being extracted from cells. In the laminated layer, IP6 was present in association with calcium, and accounted for up to 15% of the total dry mass of the HCW. IP6 was not detected in any other structures or stages of the parasite. Our results imply that IP6 is secreted by the larval stage of the parasite in a polarized fashion towards the interface with the host. This is the first report of the secretion of IP6, and the possible implications beyond the biology of E. granulosus are discussed.

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Inefficient and abortive classical complement pathway activation by the calcium inositol hexakisphosphate component of the Echinococcus granulosus laminated layer

Immunobiology ◽

10.1016/j.imbio.2019.05.009 ◽

2019 ◽

Vol 224 (5) ◽

pp. 710-719 ◽

Cited By ~ 2

Author(s):

Anabella A. Barrios ◽

Leticia Grezzi ◽

Sebastián Miles ◽

Mara Mariconti ◽

Gustavo Mourglia-Ettlin ◽

...

Keyword(s):

Echinococcus Granulosus ◽

Complement Pathway ◽

Inositol Hexakisphosphate ◽

Classical Complement Pathway ◽

Pathway Activation ◽

Laminated Layer ◽

Classical Complement

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Molecular characterization and serodiagnostic potential of Echinococcus granulosus hexokinase

Parasites & Vectors ◽

10.1186/s13071-021-04606-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Qi Xin ◽

Miaomiao Yuan ◽

Wei Lv ◽

Huanping Li ◽

Xiaoxia Song ◽

...

Keyword(s):

Molecular Characterization ◽

Echinococcus Granulosus ◽

Larval Stage ◽

Sensu Stricto ◽

Enzyme Linked Immunosorbent Assay ◽

Survival And Development ◽

Key Enzyme ◽

Life Threatening ◽

Fluorescence Immunohistochemistry ◽

Laminated Layer

Abstract Background Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus (sensu stricto), is a life-threatening but neglected zoonosis. Glycolytic enzymes are crucial molecules for the survival and development of E. granulosus. The aim of this study was to investigate the molecular characterization, immunogenicity, tissue distribution and serodiagnostic potential of E. granulosus hexokinase (EgHK), the first key enzyme in the glycolytic pathway. Methods EgHK was cloned and expressed in Escherichia coli. Specific serum antibodies were evaluated in mice immunized with recombinant EgHK (rEgHK). The location of EgHK in the larval stage of E. granulosus was determined using fluorescence immunohistochemistry, and the potential of rEgHK as a diagnostic antigen was investigated in patients with CE using indirect enzyme-linked immunosorbent assay (ELISA). Results Recombinant EgHK could be identified in the sera of patients with CE and in mouse anti-rEgHK sera. High titers of specific immunoglobulin G were induced in mice after immunization with rEgHK. EgHK was mainly located in the tegument, suckers and hooklets of protoscoleces and in the germinal layer and laminated layer of the cyst wall. The sensitivity and specificity of the rEgHK-ELISA reached 91.3% (42/46) and 87.8% (43/49), respectively. Conclusions We have characterized the sequence, structure and location of EgHK and investigated the immunoreactivity, immunogenicity and serodiagnostic potential of rEgHK. Our results suggest that EgHK may be a promising candidate for the development of vaccines against E. granulosus and an effective antigen for the diagnosis of human CE.

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In vitro immunoregulatory activity and anti-inflammatory effect of Echinococcus granulosus laminated layer

Acta Tropica ◽

10.1016/j.actatropica.2021.105886 ◽

2021 ◽

Vol 218 ◽

pp. 105886

Author(s):

Sara Benazzouz ◽

Manel Amri ◽

Junhua Wang ◽

Samia Bouaziz ◽

Fahima Ameur ◽

...

Keyword(s):

Echinococcus Granulosus ◽

Anti Inflammatory ◽

Laminated Layer ◽

Inflammatory Effect

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Response patterns in adventitial layer of Echinococcus granulosus sensu stricto cysts from naturally infected cattle and sheep

Veterinary Research ◽

10.1186/s13567-021-00936-8 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Christian Hidalgo ◽

Caroll Stoore ◽

María Soledad Baquedano ◽

Ismael Pereira ◽

Carmen Franco ◽

...

Keyword(s):

Immune Response ◽

Echinococcus Granulosus ◽

Cystic Echinococcosis ◽

Direct Contact ◽

Sensu Stricto ◽

Response Patterns ◽

Granulomatous Reaction ◽

Adventitial Layer ◽

Laminated Layer ◽

Cattle And Sheep

AbstractCystic echinococcosis is a zoonotic disease caused by the metacestode of Echinococcus granulosus sensu lato. The disease is characterized by the development of cystic structures inside viscera of the intermediate host, mainly liver and lungs. These cysts are formed by three layers: germinal, laminated, and adventitial layer, the latter being the local host immune response. Metacestodes that develop protoscoleces, the infective stage to the definitive host, are termed fertile, whereas cysts that do not produce protoscoleces are termed non-fertile. Sheep usually harbor fertile cysts while cattle usually harbor non-fertile cysts. Adventitial layers with fibrotic resolution are associated to fertile cysts, whereas a granulomatous reaction is associated with non-fertile cysts. The aim of this study was to analyze cellular distribution in the adventitial layer of fertile and non-fertile E. granulosus sensu stricto cysts found in liver and lungs of cattle and sheep. A total of 418 cysts were analyzed, 203 from cattle (8 fertile and 195 non-fertile) and 215 from sheep (64 fertile and 151 non-fertile). Fertile cysts from cattle showed mixed patterns of response, with fibrotic resolution and presence of granulomatous response in direct contact with the laminated layer, while sheep fertile cysts always displayed fibrotic resolution next to the laminated layer. Cattle non-fertile cysts display a granulomatous reaction in direct contact with the laminated layer, whereas sheep non-fertile cysts display a granulomatous reaction, but in direct contact with the fibrotic resolution. This shows that cattle and sheep cystic echinococcosis cysts have distinct local immune response patterns, which are associated to metacestode fertility.

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myo-Inositol hexakisphosphate is a major component of an extracellular structure in the parasitic cestode Echinococcus granulosus

Biochemical Journal ◽

10.1042/0264-6021:3620297 ◽

2002 ◽

Vol 362 (2) ◽

pp. 297 ◽

Cited By ~ 17

Author(s):

Florencia IRIGOÍN ◽

Fernando FERREIRA ◽

Cecilia FERNÁNDEZ ◽

Robert B. SIM ◽

Alvaro DÍAZ

Keyword(s):

Echinococcus Granulosus ◽

Inositol Hexakisphosphate

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Antibody response to glycan antigens of hydatid cyst fluid, laminated layer and protoscolex of Echinococcus granulosus

Medical Journal of the Islamic Republic of Iran ◽

10.18869/mjiri.31.12 ◽

2017 ◽

Vol 31 (1) ◽

pp. 66-70

Author(s):

Raheleh Rafiei Sefiddashti ◽

Seyedeh Maryam Sharafi ◽

Soltan Ahmad Ebrahimi ◽

Lame Akhlaghi ◽

Ali Moosavi ◽

...

Keyword(s):

Antibody Response ◽

Hydatid Cyst ◽

Echinococcus Granulosus ◽

Cyst Fluid ◽

Laminated Layer ◽

Hydatid Cyst Fluid

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Roles of Immune Cells in the Concurrence of Echinococcus Granulosus Infection and Hepatocellular Carcinoma

10.21203/rs.3.rs-98853/v1 ◽

2020 ◽

Author(s):

Aimaiti Yasen ◽

Bo Ran ◽

Maolin Wang ◽

Guodong Lv ◽

Renyong Lin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

T Cell ◽

Immune Responses ◽

Nk Cells ◽

Echinococcus Granulosus ◽

Immune Cells ◽

Hepg2 Cells ◽

Control Group ◽

Cell Markers ◽

Hepg2 Cell Lines

Abstract Background/aims: Immune cells are pivotal players in the immune responses against both parasitic infection and malignancies. Substantial evidence demonstrated that there may exist possible relationship between Echinococcus granulosus (E.granulosus) infection and hepatocellular carcinoma (HCC) development. Thus, this study aimed to observe crucial roles of immune cells in the formation of subcutaneous lesions after transplanting HepG2 cell lines with or without E.granulosus protoscoleces (PSCs).Methods: HepG2 cell lines were subcutaneously injected into nude mice in the control group. In the co-transplantation group, HepG2 cells were subcutaneously co-injected with high dosage of E.granulosus PSCs. From the 25th day of transplantation, volume of subcutaneous lesions was measured every four days, which were removed at the 37th day for further studies. Basic pathological and functional changes were observed. Moreover, expression of Ki67, Bal-2, Caspase3, α-smooth muscle actin (α-SMA), T cell markers (CD3, CD4, CD8), PD1/PD-L1, nature killer (NK) cell markers (CD16, CD56) were further detected by immunohistochemistry.Results: Subcutaneous lesions were gradually increased in volume and there occurred pathologically heterogeneous tumor cells, which were more significant in the co-transplantation group. Compared to the control group, expression of proliferation markers Ki67 and Bcl-2 was at higher levels in the co-transplantation group. Reversely, apoptotic marker Caspase3 was highly detected in the control group, suggesting promoting effects of E.granulosus PSCs on HCC development. Interestingly, subcutaneous lesions of the co-transplantation group were more functional in synthesizing and storing glycogen. Collagen and α-SMA+ cells were also at higher levels in the co-transplantation group than those in the control group. Most importantly, co-transplantation of HepG2 cells with E.granulosus PSCs led to significant increase in the expression of T cell markers (CD3, CD4 and CD8), immune inhibitory checkpoint PD1/PD-L1 and NK cells markers (CD16 and CD56). Conclusions: E.granulosus may have promoting effects on HCC development, which was closely associated with the immune responses of T cells and NK cells.

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Biological Responses of Onion-Shaped Carbon Nanoparticles

Nanomaterials ◽

10.3390/nano9071016 ◽

2019 ◽

Vol 9 (7) ◽

pp. 1016 ◽

Cited By ~ 1

Author(s):

Jaehee Jang ◽

Youngjun Kim ◽

Jangsun Hwang ◽

Yonghyun Choi ◽

Masayoshi Tanaka ◽

...

Keyword(s):

Immune Cells ◽

Carbon Nanoparticles ◽

Carbon Nanomaterials ◽

Human Colon ◽

Oxygen Species ◽

Biological Applications ◽

Biotechnological Applications ◽

Animal Cells ◽

Biological Responses ◽

Human Immune

Nanodiamonds are emerging as new nanoscale materials because of their chemical stability, excellent crystallinity, and unique optical properties. In this study, the structure of nanodiamonds was engineered to produce carbon nano-onion particles (CNOs) with multiple layers. Following a series of physicochemical characterizations of the CNOs, various evaluations for biological responses were conducted for potential biotechnological applications of the CNOs. The possibility of biological applications was first confirmed by assessment of toxicity to animal cells, evaluation of hemolysis reactions, and evaluation of reactive oxygen species. In addition, human immune cells were evaluated for any possible induction of an immune response by CNOs. Finally, the toxicity of CNOs to Escherichia coli present in the human colon was evaluated. CNOs have the chemical and physical properties to be a unique variety of carbon nanomaterials, and their toxicity to animal and human cells is sufficiently low that their biotechnological applications in the future are expected.

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