Fasciola hepatica isolates induce different immune responses in unmaturated bovine macrophages

Open access


Introduction: Fasciola hepatica (liver fluke) is a parasite of great socioeconomic importance. A number of fluke isolates have been identified; however, to date the differences between the immunomodulatory properties of different parasite isolates have not been sufficiently investigated. The aim of this study was to explore differences between the immunomodulatory properties of two F. hepatica isolates using unmaturated bovine macrophages.

Material and Methods: A cell line of bovine macrophages was stimulated with excretory/secretory products released by adult flukes from either a laboratory (Fh-WeyES) or wild (Fh-WildES) strain and subsequently subjected to microarray and ELISA analyses.

Results: Both Fh-WeyES and Fh-WildES dampened the release of interleukin-10 by bovine macrophages, but only Fh-WildES dampened the release of proinflammatory tumour necrosis factor-α. Microarray analysis revealed that Fh-WildES down- and upregulated 90 and 18 genes, respectively, when compared to Fh-WeyES.

Conclusion: The results indicated different impacts of the isolates on macrophages. A number of researchers use flukes obtained from local slaughterhouses for experiments. Our findings may explain some discrepancies between published results arising from parasite strain choice. The findings indicate that consideration should be given to the use of different strains, and open new and currently unexplored avenues in parasitology for controlling the parasite.

1. Bąska P., Norbury L.J., Wiśniewski M., Januszkiewicz K., Wędrychowicz H.: Excretory/secretory products of Fasciola hepatica but not recombinant phosphoglycerate kinase induce death of human hepatocyte cells. Acta Parasitol. 2013, 58, 215–217. doi: 10.2478/s11686-013-0126-x.

2. Bąska P., Norbury L.J., Zawistowska-Deniziak A., Wiśniewski M., Januszkiewicz K.: Excretory/secretory products from two Fasciola hepatica isolates induce different transcriptional changes and IL-10 release in LPS-activated bovine “BOMA” macrophages. Parasitol Res 2017, 116, 2775–2782. doi: 10.1007/s00436-017-5588-6.

3. Bąska P., Zawistowska-Deniziak A., Zdziarska A.M., Wasyl K., Wiśniewski M., Cywińska A., Klockiewicz M., Januszkiewicz K., Wędrychowicz H.: Fasciola hepatica - the pilot study of in vitro assessing immune response against native and recombinant antigens of the fluke. Acta Parasitol 2013, 58, 453–462. doi: 10.2478/s11686-013-0163-5.

4. Brady M.T., O’Neill S.M., Dalton J.P., Mills K.H.: Fasciola hepatica suppresses a protective Th1 response against Bordetella pertussis. Infect Immun 1999, 67, 5372–5378.

5. Collison L.W., Murphy E.J., Jolly C.A.: Glycerol-3-phosphate acyltransferase-1 regulates murine T-lymphocyte proliferation and cytokine production. Am J Physiol Cell Physiol 2008, 295, 1543–1549. doi: 10.1152/ajpcell.00371.2007.

6. Dauphinee S.M., Clayton A., Hussainkhel A., Yang C., Park Y.J., Fuller M.E., Blonder J., Veenstra T.D., Karsan A.: SASH1 is a scaffold molecule in endothelial TLR4 signaling. J Immunol 2013, 191, 892–901. doi: 10.4049/jimmunol.1200583.

7. D’Elia R., DeSchoolmeester M.L., Zeef L.A., Wright S.H., Pemberton A.D., Else K.J.: Expulsion of Trichuris muris is associated with increased expression of angiogenin 4 in the gut and increased acidity of mucins within the goblet cell. BMC Genomics 2009, 10, 492. doi: 10.1186/1471-2164-10-492.

8. Fairweather I.: Liver fluke isolates: a question of provenance. Vet Parasitol 2011, 176, 1–8.

9. Finlay C.M., Stefanska A.M., Coleman M.M., Jahns H., Cassidy J.P., McLoughlin R.M., Mills K.H.G.: Secreted products of Fasciola hepatica inhibit the induction of T cell responses that mediate allergy. Parasite Immunol 2017, 39. doi: 10.1111/pim.12460.

10. Flynn R.J., Mulcahy G., Welsh M., Cassidy J.P., Corbett D., Milligan C., Andersen P., Strain S., McNair J.: Co-infection of cattle with Fasciola hepatica and Mycobacterium bovisimmunological consequences. Transbound Emerg Dis 2009, 56, 269–274. doi:10.1111/j.1865-1682.2009.01075.x

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

12. Fu Y., Chryssafidis A.L., Browne J.A., O’Sullivan J., McGettigan P.A., Mulcahy G.: Transcriptomic study on ovine immune responses to Fasciola hepatica infection. PLoS Negl Trop Dis 2016, 10, e0005015.

13. Haçariz O., Sayers G., Flynn R.J., Lejeune A., Mulcahy G.: IL-10 and TGF-beta1 are associated with variations in fluke burdens following experimental fasciolosis in sheep. Parasite Immunol 2009, 31, 613–622.

14. Hamilton C.M., Dowling D.J., Loscher C.E., Morphew R.M., Brophy P.M., O’Neill S.M.: The Fasciola hepatica tegumental antigen suppresses dendritic cell maturation and function. Infect Immun. 2009, 77, 2488–2498. doi: 10.1128/IAI.00919-08.

15. Hill R.D., Gouffon J.S., Saxton A.M., Su C.: Differential gene expression in mice infected with distinct Toxoplasma strains. Infect Immun 2012, 80, 968–974. doi:10.1128/IAI.05421-11.

16. Huang da W., Sherman B.T., Lempicki R.A.: Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009, 37, 1–13.

17. Jimbo S., Suleman M., Maina T., Prysliak T., Mulongo M., Perez-Casal J.: Effect of Mycoplasma bovis on bovine neutrophils. Vet Immunol Immunopathol. 2017, 188, 27–33. doi: 10.1016/j.vetimm.2017.04.011.

18. Kraft S., Fleming T., Billingsley J.M., Lin S.Y., Jouvin M.H., Storz P., Kinet J.P.: Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo. J Exp Med 2005, 201, 385–396.

19. Lund M.E., O’Brien B.A., Hutchinson A.T., Robinson M.W., Simpson A.M., Dalton J.P., Donnelly S.: Secreted proteins from the helminth Fasciola hepatica inhibit the initiation of autoreactive T cell responses and prevent diabetes in the NOD mouse. PLoS One 2014, 9, e86289. doi: 10.1371/journal.pone.0086289.

20. McNulty S.N., Tort J.F., Rinaldi G., Fischer K., Rosa B.A., Smircich P., Fontenla S., Choi Y.J., Tyagi R., Hallsworth-Pepin K., Mann V.H., Kammili L., Latham P.S., Dell’Oca N., Dominguez F., Carmona C., Fischer P.U., Brindley P.J., Mitreva M.: Genomes of Fasciola hepatica from the Americas reveal colonization with Neorickettsia Endobacteria related to the agents of Potomac Horse and Human Sennetsu Fevers. PLoS Genet. 2017, 6, 13, e1006537. doi: 10.1371/journal.pgen.1006537.

21. Mi H., Poudel S., Muruganujan A., Casagrande J.T., Thomas P.D.: PANTHER version 10: expanded protein families and functions, and analysis tools. Nucleic Acids Res 2016, 44, 336–342. doi: 10.1093/nar/gkv1194.

22. Montojo J., Zuberi K., Rodriguez H., Bader G.D., Morris Q.: GeneMANIA: Fast gene network construction and function prediction for Cytoscape. F1000Res 2014, 1, 3:153. doi: 10.12688/f1000research.4572.1.eCollection 2014.

23. Morrison L.J., McLellan S., Sweeney L., Chan C.N., MacLeod A., Tait A., Turner C.M.: Role for parasite genetic diversity in differential host responses to Trypanosoma brucei infection. Infect Immun 2010, 78, 1096–1108. doi: 10.1128/IAI.00943-09.

24. Norbury L.J., Beckham S., Pike R.N., Grams R., Spithill T.W., Fecondo J.V., Smooker P.M.: Adult and juvenile Fasciola cathepsin L proteases: different enzymes for different roles. Biochimie 2011, 93, 604–611. doi: 10.1016/j.biochi.2010.12.004.

25. Park J.H., Jeong D.Y., Peyrin-Biroulet L., Eisenhut M., Shin J.I.: Insight into the role of TSLP in inflammatory bowel diseases. Autoimmun Rev 2017, 16, 55–63. doi: 10.1016/j.autrev.2016.09.014.

26. Risco A., del Fresno C., Mambol A., Alsina-Beauchamp D., MacKenzie K.F., Yang H.T., Barber D.F., Morcelle C., Arthur J.S., Ley S.C., Ardavin C., Cuenda A.: p38γ and p38δ kinases regulate the Toll-like receptor 4 (TLR4)-induced cytokine production by controlling ERK1/2 protein kinase pathway activation. Proc Natl Acad Sci USA 2012, 109, 11200–11205. doi: 10.1073/pnas.1207290109.

27. Rodríguez E., Carasi P., Frigerio S., da Costa V., van Vliet S., Noya V., Brossard N., van Kooyk Y., García-Vallejo J.J., Freire T.: Fasciola hepatica immune regulates CD11c+ cells by interacting with the macrophage Gal/GalNAc lectin. Front Immunol 2017, 8, 264. doi: 10.3389/fimmu.2017.00264. eCollection 2017.

28. Siegmund K., Klepsch V., Hermann-Kleiter N., Baier G.: Proof of principle for a T lymphocyte intrinsic function of coronin 1A. J Biol Chem 2016, 291, 22086–22092.

29. Verbanac D., Zanetti M., Romeo D.: Chemotactic and protease-inhibiting activities of antibiotic peptide precursors. FEBS Lett 1993, 317, 255–258.

30. Wang Y., Zhu J., Zhang L., Zhang Z., He L., Mou Y., Deng Y., Cao Y., Yang P., Su Y., Zhao J., Zhang S., Yu Q., Hu J., Chen Z., Ning Q., Xiang X., Xu Y., Wang C.Y., Xiong W.: Role of C/EBP homologous protein and endoplasmic reticulum stress in asthma exacerbation by regulating the IL-4/signal transducer and activator of transcription 6/transcription factor EC/IL-4 receptor α positive feedback loop in M2 macrophages. J Allergy Clin Immunol 2017, 140, 1550–1561.e8. doi: 10.1016/j.jaci.2017.01.024.

Journal of Veterinary Research

formerly Bulletin of the Veterinary Institute in Pulawy

Journal Information

IMPACT FACTOR J Vet Res 2018: 0,829
5-year IMPACT FACTOR: 0,938

CiteScore 2018: 0.68

SCImago Journal Rank (SJR) 2018: 0.291
Source Normalized Impact per Paper (SNIP) 2018: 0.501


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 324 324 65
PDF Downloads 148 148 24