Skip to main content

Advertisement

Springer Nature Link
Log in

A mucin-like peptide from Fasciola hepatica induces parasite-specific Th1-type cell immunity

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Fasciolosis, caused by the liver fluke Fasciola hepatica, is a major parasitic disease of livestock that causes significant economic losses worldwide. Although drugs are effective against liver flukes, they do not prevent reinfection, and continuous treatment is costly. Moreover, resistant fluke strains are emerging. In this context, vaccination is a good alternative since it provides a cost-effective long-term prevention strategy to control fasciolosis. In this paper, we evaluate the Fhmuc peptide as a potential vaccine against fasciolosis. This peptide derives from a mucin-like protein highly expressed in the infective stage of Fasciola hepatica. Mucin-like molecules expressed by parasites can contribute to several infection processes by protecting the parasite from host proteases and recognition by the immune system. We show that the Fhmuc peptide induces Th1-like immune responses specific for F. hepatica excretion-secretion products (FhESP) with a high production of IFNγ. We also investigated whether this peptide could protect animals from infection, and present preliminary data indicating that animals treated with Fhmuc exhibited reduced liver damage compared to non-immunised animals and that this protection was associated with a recruitment of B and T lymphocytes in the peritoneum, as well as eosinophils and mature dendritic cells. These results suggest that the mucin-like peptide Fhmuc could constitute a potential vaccine candidate against fasciolosis and pave the way towards the development of vaccines against parasites.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

Abbreviations

DCs:

Dendritic cells

HLN:

Hepatic lymph node

MHC:

Major histocompatibility complex

References

  • Buscaglia C, Campo V, Frasch A, Di Noia J (2006) Trypanosoma cruzi surface mucins: host-dependent coat diversity. Nat Rev Microbiol 4:229–236

    Article  CAS  PubMed  Google Scholar 

  • Cancela M, Ruétalo N, Dell’Oca N, da Silva E, Smircich P, Rinaldi G, Roche L, Carmona C, Alvarez-Valín F, Zaha A, Tort J (2010) Survey of transcripts expressed by the invasive juvenile stage of the liver fluke Fasciola hepatica. BMC Genomics 11:227

    Article  PubMed Central  PubMed  Google Scholar 

  • Cancela M, Santos GB, Carmona C, Ferreira HB, Tort JF, Zaha A (2015) Fasciola hepatica mucin-encoding gene: expression, variability and its potential relevance in host-parasite relationship. Parasitology 1–9. doi:10.1017/S0031182015001134

  • Cardoso FC, Macedo GC, Gava E, Kitten GT, Mati VL, de Melo AL, Caliari MV, Almeida GT, Venancio TM, Verjovski-Almeida S, Oliveira SC (2008) Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection. PLoS Negl Trop Dis 2(10):e308. doi:10.1371/journal.pntd.0000308

    Article  PubMed Central  PubMed  Google Scholar 

  • Cervi L, Borgonovo J, Egea M, Chiapello L, Masih D (2004) Immunization of rats against Fasciola hepatica using crude antigens conjugated with Freund’s adjuvant or oligodeoxynucleotides. Vet Immunol Immunopathol 97(1-2):97–104

    Article  CAS  PubMed  Google Scholar 

  • Claridge J, Diggle P, McCann C, Mulcahy G, Flynn R, McNair J, Strain S, Welsh M, Baylis M, Williams D (2012) Fasciola hepatica is associated with the failure to detect bovine tuberculosis in dairy cattle. Nat Commun 3:doi:10.1038/ncomms1840

  • Donnelly S, Stack S, O’Neill S, Sayed A, Williams D, Dalton J (2008) Helminth 2-Cys peroxiredoxin drives Th2 responses through a mechanism involving alternatively activated macrophages. FASEB J 22:4022–4032

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fairweather I (2009) Triclabendazole progress report, 2005-2009: an advancement of learning? J Helminthol 83:139–150

    Article  CAS  PubMed  Google Scholar 

  • Fairweather I (2011) Reducing the future threat from (liver) fluke: realistic prospect or quixotic fantasy? Vet Parasitol 180:133–143

    Article  PubMed  Google Scholar 

  • Flynn R, Mulcahy G (2008) The roles of IL-10 and TGF-beta in controlling IL-4 and IFN-gamma production during experimental Fasciola hepatica infection. Int J Parasitol 38:1673–1680

    Article  CAS  PubMed  Google Scholar 

  • Flynn R, Mannion C, Golden O, Hacariz O, Mulcahy G (2007) Experimental Fasciola hepatica infection alters responses to tests used for diagnosis of bovine tuberculosis. Infect Immun 75:1373–1381

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Garza-Cuartero L, Garcia-Campos A, Zintl A, Chryssafidis A, O’Sullivan J, Sekiya M, Mulcahy G (2014) The worm turns: trematodes steering the course of co-infections. Vet Pathol 51(2):385–392. doi:10.1177/0300985813519655

    Article  CAS  PubMed  Google Scholar 

  • Hillyer GV (2005) Fasciola antigens as vaccines against fascioliasis and schistosomiasis. J Helminthol 79(3):241–247

    Article  CAS  PubMed  Google Scholar 

  • Keiser J, Engels D, Büscher G, Utzinger J (2005) Triclabendazole for the treatment of fascioliasis and paragonimiasis. Expert Opin Investig Drugs 14:1513–1526

    Article  CAS  PubMed  Google Scholar 

  • Khan M, Sajid M, Riaz H, Ahmad N, He L, Shahzad M, Hussain A, Khan M, Iqbal Z, Zhao J (2013) The global burden of fasciolosis in domestic animals with an outlook on the contribution of new approaches for diagnosis and control. Parasitol Res 112:2421–230

    Article  PubMed  Google Scholar 

  • Lim SK (2003) Freund adjuvant induces TLR2 but not TLR4 expression in the liver of mice. Int Immunopharmacol 3(1):115–118

    Article  CAS  PubMed  Google Scholar 

  • Loukas A, Hintz M, Linder D, Mullin N, Parkinson J, Tetteh K, Maizels R (2000) A family of secreted mucins from the parasitic nematode Toxocara canis bears diverse mucin domains but shares similar flanking six-cysteine repeat motifs. J Biol Chem 275:39600–39607

    Article  CAS  PubMed  Google Scholar 

  • Maizels R (2013) Toxocara canis: molecular basis of immune recognition and evasion. Vet Parasitol 193:365–374

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Maizels R, Tetteh K, Loukas A (2000) Toxocara canis: genes expressed by the arrested infective larval stage of a parasitic nematode. Int J Parasitol 30:495–508

    Article  CAS  PubMed  Google Scholar 

  • McManus D, Dalton J (2006) Vaccines against the zoonotic trematodes Schistosoma japonicum, Fasciola hepatica and Fasciola gigantica. Parasitology 133:S43–S61

    Article  PubMed  Google Scholar 

  • Molina-Hernandez V, Mulcahy G, Perez J, Martinez-Moreno A, Donnelly S, O’Neill SM, Dalton JP, Cwiklinski K (2015) Fasciola hepatica vaccine: we may not be there yet but we’re on the right road. Vet Parasitol 208(1-2):101–111. doi:10.1016/j.vetpar.2015.01.004

    Article  PubMed Central  PubMed  Google Scholar 

  • Noya V, Rodríguez E, Cervi L, Giacomini C, Brossard N, Chiale C, Carmona C, Freire T (2014) Modulation of dendritic cell maturation by Fasciola hepatica: Implications of glycans and mucins for vaccine development. J Vaccines Vaccin 5(4):233. doi:10.4172/2157-7560.1000233

    Google Scholar 

  • O’Neill S, Brady M, Callanan J, Mulcahy G, Joyce P, Mills K, Dalton J (2000) Fasciola hepatica infection downregulates Th1 responses in mice. Parasite Immunol 22:147–155

    Article  PubMed  Google Scholar 

  • Perrin C, Lepesant J, Roger E, Duval D, Fneich S, Thuillier V, Alliene J, Mitta G, Grunau C, Cosseau C (2013) Schistosoma mansoni mucin gene (SmPoMuc) expression: epigenetic control to shape adaptation to a new host. PLoS Pathog 9:e1003571

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Piedrafita D, Estuningsih E, Pleasance J, Prowse R, Raadsma HW, Meeusen EN, Spithill TW (2007) Peritoneal lavage cells of Indonesian thin-tail sheep mediate antibody-dependent superoxide radical cytotoxicity in vitro against newly excysted juvenile Fasciola gigantica but not juvenile Fasciola hepatica. Infect Immun 75(4):1954–1963. doi:10.1128/IAI.01034-06

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Piedrafita D, Spithill T, Smith R, Raadsma H (2010) Improving animal and human health through understanding liver fluke immunology. Parasite Immunol 32:572–581

    CAS  PubMed  Google Scholar 

  • Pleasance J, Wiedosari E, Raadsma HW, Meeusen E, Piedrafita D (2011) Resistance to liver fluke infection in the natural sheep host is correlated with a type-1 cytokine response. Parasite Immunol 33(9):495–505. doi:10.1111/j.1365-3024.2011.01305.x

    Article  CAS  PubMed  Google Scholar 

  • Roger E, Gourbal B, Grunau C, Pierce R, Galinier R, Mitta G (2008) Expression analysis of highly polymorphic mucin proteins (Sm PoMuc) from the parasite Schistosoma mansoni. Mol Biochem Parasitol 157:217–227

    Article  CAS  PubMed  Google Scholar 

  • Rojas-Caraballo J, Lopez-Aban J, Perez del Villar L, Vizcaino C, Vicente B, Fernandez-Soto P, del Olmo E, Patarroyo MA, Muro A (2014) In vitro and in vivo studies for assessing the immune response and protection-inducing ability conferred by Fasciola hepatica-derived synthetic peptides containing B- and T-cell epitopes. PLoS One 9(8):e105323. doi:10.1371/journal.pone.0105323

    Article  PubMed Central  PubMed  Google Scholar 

  • Rojo-Vázquez F, Meana A, Valcárcel F, Martínez-Valladares M (2012) Update on trematode infections in sheep. Vet Parasitol 189:15–38

    Article  PubMed  Google Scholar 

  • Steinman RM (2012) Decisions about dendritic cells: past, present, and future. Annu Rev Immunol 30:1–22. doi:10.1146/annurev-immunol-100311-102839

    Article  CAS  PubMed  Google Scholar 

  • Swartz JM, Dyer KD, Cheever AW, Ramalingam T, Pesnicak L, Domachowske JB, Lee JJ, Lee NA, Foster PS, Wynn TA, Rosenberg HF (2006) Schistosoma mansoni infection in eosinophil lineage-ablated mice. Blood 108(7):2420–2427. doi:10.1182/blood-2006-04-015933

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Theodoropoulos G, Hicks SJ, Corfield AP, Miller BG, Carrington SD (2001) The role of mucins in host-parasite interactions: Part II - helminth parasites. Trends Parasitol 17(3):130–135

    Article  CAS  PubMed  Google Scholar 

  • Toet H, Piedrafita DM, Spithill TW (2014) Liver fluke vaccines in ruminants: strategies, progress and future opportunities. Int J Parasitol 44(12):915–927. doi:10.1016/j.ijpara.2014.07.011

    Article  CAS  PubMed  Google Scholar 

  • Van Milligen FJ, Cornelissen JB, Bokhout BA (1999) Protection against Fasciola hepatica in the intestine is highly correlated with eosinophil and immunoglobulin G1 responses against newly excysted juveniles. Parasite Immunol 21(5):243–251

    Article  PubMed  Google Scholar 

  • Walsh K, Brady M, Finlay C, Boon L, Mills K (2009) Infection with a helminth parasite attenuates autoimmunity through TGF-beta-mediated suppression of Th17 and Th1 responses. J Immunol 183:1577–1586

    Article  CAS  PubMed  Google Scholar 

  • Zimmerman GL, Kerkvliet NI, Brauner JA, Cerro JE (1983) Modulation of host immune responses by Fasciola hepatica: responses by peripheral lymphocytes to mitogens during liver fluke infections of sheep. J Parasitol 69(3):473–477

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are especially thankful to the abattoirs ‘Frigorífico Carrasco’ and ‘Frigrorífico Sarubbi’ for their help with the collection of worms.

Author information

Authors and Affiliations

  1. UdelaR, Facultad de Medicina, Departamento de Inmunobiología, Group of Immunomodulation and Vaccine Development, Gral. Flores 2125, CP11800, Montevideo, Uruguay

    Verónica Noya, Natalie Brossard, Ernesto Rodríguez, Carolina Chiale & Teresa Freire

  2. UdelaR, Facultad de Ciencias, Instituto de Higiene, Departamento de Biología Celular y Molecular, Unidad de Biología Parasitaria, Av. A. Navarro 3051, CP11600, Montevideo, Uruguay

    Patricia Berasaín & Carlos Carmona

  3. Udelar, Facultad de Medicina, Hospital de Clínicas, Cátedra de Anatomía Patológica, Av. Italia 2590, CP11600, Montevideo, Uruguay

    Daniel Mazal

Authors
  1. Verónica Noya
    View author publications

    Search author on:PubMed Google Scholar

  2. Natalie Brossard
    View author publications

    Search author on:PubMed Google Scholar

  3. Patricia Berasaín
    View author publications

    Search author on:PubMed Google Scholar

  4. Ernesto Rodríguez
    View author publications

    Search author on:PubMed Google Scholar

  5. Carolina Chiale
    View author publications

    Search author on:PubMed Google Scholar

  6. Daniel Mazal
    View author publications

    Search author on:PubMed Google Scholar

  7. Carlos Carmona
    View author publications

    Search author on:PubMed Google Scholar

  8. Teresa Freire
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Teresa Freire.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by grants from the Agencia Nacional de Investigación e Innovación (PR-FCE-2009-1-2782, ANII, Uruguay) and Comisión Sectorial de Investigación Científica (CSIC, Universidad de la República, Uruguay). VN and ER were supported by CSIC and ANII, respectively.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

Supplementary Figure 1. Immunophenotyping of lymphoid or myeloid cells from Fhmuc-immunised animals in absence of infection. Immunophenotype of splenocytes and PECs from Fhmuc-immunised (20 μg/mouse) or PBS-treated mice. The immunisation was i.p. on days 0 in Complete Freund’s adjuvant followed by two additional injections at days 14 and 28 in Incomplete Freund’s adjuvant. Three weeks after infection, animals were sacrificed and spleen, HLN or PECs were removed. Cells were stained with different fluorochrome-conjugated specific antibodies and analysed by flow cytometry. Different myeloid (A) or lymphoid (B) cell populations were evaluated. Thirty thousand events were collected and gated on FSC vs SSC dot plot. Results are shown as the percentage of cells in the spleen expressed as the mean value of eight replicates (±SD, indicated by error bars) and are representative of two different experiments. Asterisks (*) represent statistically significant differences (p < 0.05).

Supplementary Figure 2. Amino acid sequence alignment of the Fhmuc peptide and the B5 peptide from cathepsin B. Sequence alignment of the Fhmuc peptide and the B5 peptide from Cathepsin B3 (GenBank accession number ABU62925.1 (sequence ISEIRDQSSTSSTWAVSSAS). The alignment was performed by ClustalW. Gaps have been inserted to maximise amino acid identity. Fully conserved residues are marked with (*), residues with strongly similar properties with (:) and weakly similar properties with (.). The B5 peptide sequence was reported by Rojas-Caraballo et al. (2014). (PDF 217 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Noya, V., Brossard, N., Berasaín, P. et al. A mucin-like peptide from Fasciola hepatica induces parasite-specific Th1-type cell immunity. Parasitol Res 115, 1053–1063 (2016). https://doi.org/10.1007/s00436-015-4834-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-015-4834-z

Keywords