Negligible elongation of mucin glycans with Gal β1-3 units distinguishes the laminated layer of Echinococcus multilocularis from that of Echinococcus granulosus

Puerto, Lucía del; Rovetta, Romina; Navatta, Marco; Fontana, Carolina; Lin, Gerardo; Moyna, Guillermo; Dematteis, Sylvia; Brehm, Klaus; Koziol, Uriel; Ferreira, Fernando; Díaz, Álvaro

doi:10.1016/j.ijpara.2015.12.009

Cited by 16 publications

(18 citation statements)

References 44 publications

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“…Previous studies have shown that the E. multilocularis LL is probably formed by a single type of mucin backbone, while a second apomucin subfamily additionally contributes to E. granulosus s.s . LL 34,35 . In CE, the LL seems to prevent the exogenic budding that characterizes AE lesions; in addition, as complement-activating antibodies are part of the protective immune response 36 , LL represents a first barrier against the host’s immune attack; in addition, we may hypothesize that its composition may attract and trigger the activation of the host’s cells involved in the development of the AL, which constitutes a second barrier when the cyst is fully established 12 .…”

Section: Discussionmentioning

confidence: 99%

The local immune response during Echinococcus granulosus growth in a quantitative hepatic experimental model

Zhang

et al. 2019

Sci Rep

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The local immune mechanisms responsible for the establishment and development of Echinococcus granulosus sensu stricto infection in the liver, have been little explored. We developed a suitable experimental model that mimics naturally infected livers using portal injection of protoscoleces. Opposite to Echinococcus multilocularis infection which is dose-dependent, fully mature hydatid cysts can be established in the liver whatever the injection dose; although most of the infection sites were seen at the establishment phase as inflammatory granulomas associated with fibrosis, they never matured into cysts. At the establishment phase, a strong immune response was composed of T and B cells, with T1-type, T2-type cells and cytokines and IL-10-secreting CD8+ T cells in the liver. At the established phase, results suggested a local production of antibodies by B cells, and an involvement of NK and NKT cells. Infection outcome and local immune response in the liver, were different in the mouse models of Echinococcus granulosus sensu stricto and Echinococcus multilocularis respectively; however, only early specificities at the microenvironment level might explain the major differences found between the lesions induced by the two species. Our quantitative experimental model appears fully appropriate to further study this microenvironment and its relationship with each cestode species.

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Section: Discussionmentioning

confidence: 99%

The local immune response during Echinococcus granulosus growth in a quantitative hepatic experimental model

Zhang

et al. 2019

Sci Rep

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“…While emfr1 expression levels were equal in MV when compared to MV-HU and MV-BI, both emfr2 and emfr3 transcripts were significantly reduced in MV-HU and MV-BI (S4 Fig). This indicated that emfr1 does not have a typical stem cell-specific expression pattern whereas emfr2 and emfr3 could be expressed in the parasite’s stem cells or their immediate progeny (since HU- and BI 2536-treatment has to be carried out for at least one week [6,34]).…”

Section: Resultsmentioning

confidence: 99%

“…qRT-PCR experiments have been performed as previously described by del Puerto et al [34] with several modifications. Briefly, RNA samples were prepared with TRI-reagent and the DirectzolTM RNA Mini Prep Kit (Zymo Research, USA).…”

Section: Methodsmentioning

confidence: 99%

“…qRT-PCRs were then performed using primers Forward F_emfr1_qPCR (5’-CCG TAT GAA GGG AAA TGG TCG TGT T-3’) and Reverse R_emfr1_qPCR (5’-TGG TGA ATC GCC AAG GCT GAA A-3’) for emfr1 , Forward F_emfr2_qPCR (5’-GGG AAT TTC CAA GGT CAT CAG GGA C-3’) and Reverse R_emfr2_qPCR (5’-ATC GTG GGG GCA CAA CAT AAT TGC-3’) for emfr2 , as well as Forward F_emfr3_qPCR (5’-GTC TAC CTT GAG GAA ATT GCT GTG GTC-3’) and Reverse R_emfr3_qPCR (5’-CGT GAG GAA TGA CGC AGG C-3’) for emfr3 . As a control gene for normalization, the constitutively expressed gene elp was used with primers as described previously [34]. qRT-PCR conditions and primer amplification efficiency control experiments were performed essentially as previously described [34].…”

Section: Methodsmentioning

confidence: 99%

“…As a control gene for normalization, the constitutively expressed gene elp was used with primers as described previously [34]. qRT-PCR conditions and primer amplification efficiency control experiments were performed essentially as previously described [34]. The relative expression of emfr genes in each sample was estimated using the delt-delta-Ct method [36], normalising with elp expression levels using the StepOne software (Thermo Fisher).…”

Section: Methodsmentioning

confidence: 99%

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The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction

et al. 2019

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BackgroundAlveolar echinococcosis (AE) is a lethal zoonosis caused by the metacestode larva of the tapeworm Echinococcus multilocularis. The infection is characterized by tumour-like growth of the metacestode within the host liver, leading to extensive fibrosis and organ-failure. The molecular mechanisms of parasite organ tropism towards the liver and influences of liver cytokines and hormones on parasite development are little studied to date.Methodology/Principal findingsWe show that the E. multilocularis larval stage expresses three members of the fibroblast growth factor (FGF) receptor family with homology to human FGF receptors. Using the Xenopus expression system we demonstrate that all three Echinococcus FGF receptors are activated in response to human acidic and basic FGF, which are present in the liver. In all three cases, activation could be prevented by addition of the tyrosine kinase (TK) inhibitor BIBF 1120, which is used to treat human cancer. At physiological concentrations, acidic and basic FGF significantly stimulated the formation of metacestode vesicles from parasite stem cells in vitro and supported metacestode growth. Furthermore, the parasite’s mitogen activated protein kinase signalling system was stimulated upon addition of human FGF. The survival of metacestode vesicles and parasite stem cells were drastically affected in vitro in the presence of BIBF 1120.Conclusions/SignificanceOur data indicate that mammalian FGF, which is present in the liver and upregulated during fibrosis, supports the establishment of the Echinococcus metacestode during AE by acting on an evolutionarily conserved parasite FGF signalling system. These data are valuable for understanding molecular mechanisms of organ tropism and host-parasite interaction in AE. Furthermore, our data indicate that the parasite’s FGF signalling systems are promising targets for the development of novel drugs against AE.

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The laminated layer: Recent advances and insights into Echinococcus biology and evolution

Díaz

Fernández

Pittini

et al. 2015

Experimental Parasitology

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The laminated layer is the unique mucin-based extracellular matrix that protects Echinococcus larvae, and thus to an important extent, shapes host-parasite relationships in the larval echinococcoses. In 2011, we published twin reviews summarizing what was known about this structure. Since then, important advances have been made. Complete genomes and some RNAseq data are now available for E. multilocularis and E. granulosus, leading to the inference that the E. multilocularis LL is probably formed by a single type of mucin backbone, while a second apomucin subfamily additionally contributes to the E. granulosus LL. Previously suspected differences between E. granulosus and E. multilocularis in mucin glycan size have been confirmed and pinned down to the virtual absence of Galβ1-3 chains in E. multilocularis. The LL carbohydrates from both species have been found to interact selectively with the Kupffer cell receptor expressed in rodent liver macrophages, highlighting the ancestral adaptations to rodents as intermediate hosts and to the liver as infection site. Finally, LL particles have been shown to possess carbohydrate-independent mechanisms profoundly conditioning non-liver-specific dendritic cells and macrophages. These advances are discussed in an integrated way, and in the context of the newly determined phylogeny of Echinococcus and its taenid relatives.

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Negligible elongation of mucin glycans with Gal β1-3 units distinguishes the laminated layer of Echinococcus multilocularis from that of Echinococcus granulosus

Cited by 16 publications

References 44 publications

The local immune response during Echinococcus granulosus growth in a quantitative hepatic experimental model

The local immune response during Echinococcus granulosus growth in a quantitative hepatic experimental model

The role of fibroblast growth factor signalling in Echinococcus multilocularis development and host-parasite interaction

The laminated layer: Recent advances and insights into Echinococcus biology and evolution

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