Fasciola hepatica miracidia: Lectin binding and stimulation of in vitro miracidium-to-sporocyst transformation

Georgieva, Katya; Georgieva, Simona; Mizinska, Y.; Stoitsova, Stoyanka

doi:10.2478/s11686-012-0007-8

Cited by 12 publications

(15 citation statements)

References 30 publications

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“…Because these lectins play important roles in innate immunity, their recognition of cercarial structures may be an inseparable part of host-parasite interactions which lead to, e.g., complement activation, opsonization, and cell adherence. They need not always represent a signal for cercarial transformation, although this was clearly demonstrated in our study with exogenous lectins, and a similar effect was observed in some other larval trematode transformations (e.g., Fasciola hepatica miracidia to mother sporocysts) [59]. …”

Section: Discussionsupporting

confidence: 59%

Changes in surface glycosylation and glycocalyx shedding in Trichobilharzia regenti (Schistosomatidae) during the transformation of cercaria to schistosomulum

et al. 2017

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The invasive larvae (cercariae) of schistosomes penetrate the skin of their definitive hosts. During the invasion, they undergo dramatic ultrastructural and physiological transitions. These changes result in the development of the subsequent stage, schistosomulum, which migrates through host tissues in close contact with host’s immune system. One of the striking changes in the transforming cercariae is the shedding of their thick tegumental glycocalyx, which represents an immunoattractive structure; therefore its removal helps cercariae to avoid immune attack. A set of commercial fluorescently labeled lectin probes, their saccharide inhibitors and monoclonal antibodies against the trisaccharide Lewis-X antigen (LeX, CD15) were used to characterize changes in the surface saccharide composition of the neuropathogenic avian schistosome Trichobilharzia regenti during the transformation of cercariae to schistosomula, both in vitro and in vivo. The effect of various lectins on glycocalyx shedding was evaluated microscopically. The involvement of peptidases and their inhibitors on the shedding of glycocalyx was investigated using T. regenti recombinant cathepsin B2 and a set of peptidase inhibitors. The surface glycocalyx of T. regenti cercariae was rich in fucose and mannose/glucose residues. After the transformation of cercariae in vitro or in vivo within their specific duck host, reduction and vanishing of these epitopes was observed, and galactose/N-acetylgalactosamine emerged. The presence of LeX was not observed on the cercariae, but the antigen was gradually expressed from the anterior part of the body in the developing schistosomula. Some lectins which bind to the cercarial surface also induced secretion from the acetabular penetration glands. Seven lectins induced the shedding of glycocalyx by cercariae, among which five bound strongly to cercarial surface; the effect could be blocked by saccharide inhibitors. Mannose-binding protein, part of the lectin pathway of the complement system, also bound to cercariae and schistosomula, but had little effect on glycocalyx shedding. Our study did not confirm the involvement of proteolysis in glycocalyx shedding.

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Section: Discussionsupporting

confidence: 59%

Changes in surface glycosylation and glycocalyx shedding in Trichobilharzia regenti (Schistosomatidae) during the transformation of cercaria to schistosomulum

et al. 2017

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“…hepatica still remained poorly characterized. Previous works have identified the presence of Gal(β1–6)Gal and GlcNAc(α1-HPO 3 -6)Gal terminating glycolipids by mass spectrometry [ 20 , 47 ], as well as glycans carrying Man, Glc, GlcNAc or GalNAc by lectin reactivity [ 17 – 19 , 48 ] both in tegument and tissues throughout the parasite. Here, we identified the presence of glycan structures containing Man/Glc, GalNAc or GlcNAc in the parasite lysate used in this study, confirming the strong binding of Man/Glc, GalNAc and GlcNAc-reactive lectins (ConA, WGA and VV, respectively).…”

Section: Discussionmentioning

confidence: 99%

“…Little is known about the glycans produced by F . hepatica , with only two recent reports describing lectin reactivity in the miracidial surface [ 17 ] or in the gut of adult flukes [ 18 – 19 ], that suggest the presence of Man and glucose (Glc) residues. Another independent work from Wuhrer and collaborators described Galβ1-6Gal-terminating glycolipids by using mass spectrometry [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Glycans from Fasciola hepatica Modulate the Host Immune Response and TLR-Induced Maturation of Dendritic Cells

Rodríguez¹,

Noya²,

Cervi

et al. 2015

PLoS Negl Trop Dis

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Helminths express various carbohydrate-containing glycoconjugates on their surface, and they release glycan-rich excretion/secretion products that can be very important in their life cycles, infection and pathology. Recent evidence suggests that parasite glycoconjugates could play a role in the evasion of the immune response, leading to a modified Th2-polarized immune response that favors parasite survival in the host. Nevertheless, there is limited information about the nature or function of glycans produced by the trematode Fasciola hepatica, the causative agent of fasciolosis. In this paper, we investigate whether glycosylated molecules from F. hepatica participate in the modulation of host immunity. We also focus on dendritic cells, since they are an important target of immune-modulation by helminths, affecting their activity or function. Our results indicate that glycans from F. hepatica promote the production of IL-4 and IL-10, suppressing IFNγ production. During infection, this parasite is able to induce a semi-mature phenotype of DCs expressing low levels of MHCII and secrete IL-10. Furthermore, we show that parasite glycoconjugates mediate the modulation of LPS-induced maturation of DCs since their oxidation restores the capacity of LPS-treated DCs to secrete high levels of the pro-inflammatory cytokines IL-6 and IL-12/23p40 and low levels of the anti-inflammatory cytokine IL-10. Inhibition assays using carbohydrates suggest that the immune-modulation is mediated, at least in part, by the recognition of a mannose specific-CLR that signals by recruiting the phosphatase Php2. The results presented here contribute to the understanding of the role of parasite glycosylated molecules in the modulation of the host immunity and might be useful in the design of vaccines against fasciolosis.

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“…Little is known about the glycans produced by F. hepatica, with only two reports describing lectin reactivity in the miracidial surface [23] or in the gut of adult flukes [24], suggesting the presence of mannose and glucose residues, and other describing Galβ1-6Gal-terminating glycolipids by mass spectrometry [25]. Also, our group has previously described, the expression of the GalNAc-O-Ser/Thr structure (known as Tn antigen) [26].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Dendritic Cell Maturation by Fasciola hepatica: Implications of Glycans and Mucins for Vaccine Development

Noya¹,

Rodríguez²,

Cervi³

et al. 2014

J Vaccines Vaccin

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Fasciola hepatica is a worldwide distributed helminth pathogen that causes great economic losses in sheep and cattle. This parasite is able to regulate the host immune response, producing high levels of IL-5 and low levels of IFNγ, as well as modulating the function of dendritic cells (DCs), mast cells or macrophages, among others. Moreover, TLR-mediated maturation of DCs can be suppressed by F. hepatica derived components. Here, we investigated the role of glycans in the modulation of LPS-induced maturation of DCs, as well as in the production of IL-5 and IFNγ by splenocytes from infected mice. We show that F. hepatica induces the recruitment to the peritoneum of semi-matured DCs, as judged by a down-regulation of MHC class II molecule expression and an increase of CD80 and CD86 expression of DCs in the peritoneum of infected animals. Furthermore, we provide evidence indicating that glycan structures from F. hepatica are responsible, at least in part, for inhibiting LPSinduced DC maturation and production of IFNγ by splenocytes from infected animals. On the other hand, we show that a mucin-like non-glycosylated peptide highly expressed in NEJ (Fhmuc) is able to synergize with LPS in inducing DC-maturation, and that it induces a T cell response specific for F. hepatica, both alone or in combination with DCs. Our data highlight the role of F. hepatica glycans in modulating the host immune response and might contribute to the design of vaccines against fasciolosis.

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Fasciola hepatica miracidia: Lectin binding and stimulation of in vitro miracidium-to-sporocyst transformation

Cited by 12 publications

References 30 publications

Changes in surface glycosylation and glycocalyx shedding in Trichobilharzia regenti (Schistosomatidae) during the transformation of cercaria to schistosomulum

Changes in surface glycosylation and glycocalyx shedding in Trichobilharzia regenti (Schistosomatidae) during the transformation of cercaria to schistosomulum

Glycans from Fasciola hepatica Modulate the Host Immune Response and TLR-Induced Maturation of Dendritic Cells

Modulation of Dendritic Cell Maturation by Fasciola hepatica: Implications of Glycans and Mucins for Vaccine Development

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