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Cited by 19Helminth infection and controlParasites and Host InteractionsImmunotherapy and Immune Responses

A mucin-like peptide from Fasciola hepatica instructs dendritic cells with parasite specific Th1-polarizing activity

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Noya, Verónica, Brossard, Natalie, Rodríguez, Ernesto, Dergan-Dylon, L. Sebastián, Carmona, Carlos, Rabinovich, Gabriel A., Freire, Teresa·2017·Scientific Reports
DOI 10.1038/srep40615PMC PMC5228188
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Abstract

Fasciolosis is a trematode zoonosis of interest in public health and cattle production. We report here the immunostimulatory effect of a 66 mer mucin-like peptide from Fasciola hepatica(Fhmuc), which synergizes with lipopolysaccharide (LPS) to promote dendritic cell (DC) maturation, endowing these cells with Th1-polarizing capacity. Exposure of DCs to Fhmuc in presence of LPS induced enhanced secretion of pro-inflammatory cytokines and expression of co-stimulatory molecules by DCs, promoting their T cell stimulatory capacity and selectively augmenting IFN-γ secretion by allogeneic T cells. Furthermore, exposure of DCs to Fhmuc augmented LPS-induced Toll-like receptor (TLR) 4 expression on the cell surface. Finally, Fhmuc-conditioned DCs induced parasite specific-adaptive immunity with increased levels of IFN-γ secreted by splenocytes from vaccinated animals, and higher parasite-specific IgG antibodies. However, Fhmuc-treated DC conferred modest protection against F. hepatica infection highlighting the potent immuno-regulatory capacity of the parasite. In summary, this work highlights the capacity of a mucin-derived peptide from F. hepatica to enhance LPS-maturation of DCs and induce parasite-specific immune responses with potential implications in vaccination and therapeutic strategies.

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  • Fhmuc, while not itself a TLR4 ligand, promotes LPS-induced TLR4 activation of DCs, enhancing Th1 cell responses, both in vitro and in vivo.

    “the 66-amino acid mucin-like polypeptide from F. hepatica (Fhmuc), while not itself a TLR4 ligand, promotes LPS-induced TLR4 activation of DCs, enhancing T helper 1 (Th1) cell responses, both in vitro and in vivo”

    From Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules (2018) · cites this paper as Noya et al., 2017

    The Results report that Fhmuc enhances LPS-induced dendritic-cell responses and Th1-like polarization in vitro, while Fhmuc/LPS-conditioned dendritic cells prime a Th1-profile response in vivo. The Methods identify Fhmuc as a 66-amino-acid peptide. However, the copy does not establish that Fhmuc is not a TLR4 ligand, and the Discussion presents stronger TLR4 signaling as a possible mechanism rather than a demonstrated effect. (LLM, conf=0.84)

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Authors
Noya, V., Brossard, N., Rodríguez, E., Dergan-Dylon, L. S., Carmona, C., Rabinovich, G. A., & Freire, T.
Affiliations
  • Universidad de la República de Uruguay (UY)
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
Corresponding author
Freire, Teresa
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-01-12
Volume
7
Issue
1
Pages
40615-40615
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep40615
PMC
PMC5228188
OpenAlex
W2576426637
Cited by
19
References
1
Citations by year
2026: 1 · 2025: 1 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 2
FWCI
3.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (acceptedVersion)
  • Americanae (AECID Library) (submittedVersion, cc-by)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
Funders
Agencia Nacional de Investigación e Innovación
Topics
  • Health Sciences › Veterinary › Small Animals › Helminth infection and control
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
Fasciola hepatica, dendritic cell maturation, Th1 polarization, lipopolysaccharide, interferon-gamma, TLR4, fascioliasis, vaccine adjuvants, T cell stimulation
MeSH terms
Animals, Antibodies, Antibodies, Helminth, Dendritic Cells, Fasciola hepatica, Female, Immunoglobulin G, Interferon-gamma, Lipopolysaccharides, Lymphocyte Activation, Mice, Inbred C57BL, Models, Biological, Parasites, Peptides, Peritoneal Cavity, Species Specificity, Spleen, Vaccination, Signal Transduction, Cytokines, NF-kappa B, Cell Polarity, Mucin-1, Th1 Cells, Inflammation Mediators, CD11c Antigen, Toll-Like Receptor 4

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