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An in vitro model to evaluate the cytokine response in Echinococcus infections

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Abstract

With the aim of proposing an alternative model to animal experimentation, we investigated cytokine production in response to antigens in an in vitro system. This is a co-culture system of healthy human leukocytes and enterocyte-like Caco-2 cells. The antigens tested, EgA31, EgTrp, and FABP1, are candidates for vaccines in infections caused by Echinococcus spp. in the gut. All three have previously been described in the protoscolex stage and belong to protein families which confer protective immunity against several helminths. In this study, we evaluate the Th1/Th2 profile (Th1: IL-12, IFN-γ; Th2: IL-6, IL-10) in response to protoscoleces, EgA31 and the mixture of EgA31, EgTrp and FABP1. No cytokine production was detected in response to protoscoleces. Neither IFN-γ nor IL-6, but a significant IL-10 and IL-12 concentration was detected in response to both types of antigens. These findings suggest that EgA31 and the mixture EgA31/EgTrp/FABP1 generated an immunogenic response associated with a mixed Th1/Th2 cytokine.

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References

  • Deplazes P, Thompson RC, Constantine CC, Penhale WJ (1994) Primary infection of dogs with Echinococcus granulosus: systemic and local (Peyer’s patches) immune responses. Vet Immunol Immunopathol 40:171–184

    Article  CAS  PubMed  Google Scholar 

  • Emery I, Liance M, Deriaud E, Vuitton DA, Houin R, Leclerc C (1996) Characterization of T-cell immune responses of Echinococcus multilocularis-infected C57BL/6J mice. Parasite Immunol 18:463–472

    CAS  PubMed  Google Scholar 

  • Esteves A, Portillo V, Ehrlich R (2003a) Genomic structure and expression of a gene coding for a new fatty acid binding protein from Echinococcus granulosus. Biochim Biophys Acta 1631:26–34

    Article  CAS  PubMed  Google Scholar 

  • Esteves A, Senorale M, Ehrlich R (2003b) A tropomyosin gene is differentially expressed in the larval stage of Echinococcus granulosus. Parasitol Res 89:501–502

    PubMed  Google Scholar 

  • Estuningsih SE, Smooker PM, Wiedosari E, Widjajanti S, Vaiano S, Partoutomo S, Spithill TW (1997) Evaluation of antigens of Fasciola gigantica as vaccines against tropical fasciolosis in cattle. Int J Parasitol 27:1419–1428

    Google Scholar 

  • Fu Y, Martinez C, Chalar C, Craig PS, Ehrlich R, Petavy AF, Bosquet G (1999) A new potent antigen from Echinococcus granulosus associated with muscles and tegument. Mol Biochem Parasitol 102:43–52

    CAS  PubMed  Google Scholar 

  • Fu Y, Saint-Andre Marchal I, Marchal T, Bosquet G, Petavy AF (2000) Cellular immune response of lymph nodes from dogs following the intradermal injection of a recombinant antigen corresponding to a 66 kDa protein of Echinococcus granulosus. Vet Immunol Immunopathol 74:195–208

    Article  CAS  PubMed  Google Scholar 

  • Gemmell MA, Lawson JR, Roberts MG (1986) Population dynamics in echinococcosis and cysticercosis: biological parameters of Echinococcus granulosus in dogs and sheep. Parasitology 92:599–620

    PubMed  Google Scholar 

  • Gottstein B, Deplazes P, Eckert J, Muller B, Schott E, Helle O, Boujon P, Wolff K, Wandeler A, Schwiete U et al. (1991) Serological (Em2-ELISA) and parasitological examinations of fox populations for Echinococcus multilocularis infections. Zentralbl Veterinarmed B 38:161–168

    CAS  PubMed  Google Scholar 

  • Goyal PK, Hermanek J, Wakelin D (1994) Lymphocyte proliferation and cytokine production in mice infected with different geographical isolates of Trichinella spiralis. Parasite Immunol 16:105–110

    CAS  PubMed  Google Scholar 

  • Heath DD (1995) Immunology of Echinococcus infections. In: Thompson RCA (ed) The biology of Echinococcus and hydatid disease. Allen and Unwin, London, pp 183–199

  • Hidalgo IJ, Raub TJ, Borchardt RT (1989) Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 96:736–749

    CAS  PubMed  Google Scholar 

  • Hillyer GV, Garcia Rosa MI, Alicea H, Hernandez A (1988) Successful vaccination against murine Schistosoma mansoni infection with a purified 12 Kd Fasciola hepatica cross-reactive antigen. Am J Trop Med Hyg 38:103–110

    CAS  PubMed  Google Scholar 

  • Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O’Garra A, Murphy KM (1993) Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 260:547–549

    CAS  PubMed  Google Scholar 

  • Ito A, Smyth JD (1987) Adulte cestodes—immunology of the lumen-dwelling cestode infections. In: Soulsby EJL (ed) Immune responses in parasitic infections: immunology, immunopathology and immunoprophylaxis, vol 2. CRC, Boca Raton, pp 115–163

  • Janssen D, Osuna A, Lazuen J, De Rycke PH (1992) Comparative cytotoxicity of secondary hydatid cysts, protoscoleces, and in vitro developed microcysts of Echinococcus granulosus. J Helminthol 66:124–131

    CAS  PubMed  Google Scholar 

  • Jenkins RE, Taylor MJ, Gilvary NJ, Bianco AE (1998) Tropomyosin implicated in host protective responses to microfilariae in onchocerciasis. Proc Natl Acad Sci U S A 95:7550–7555

    Article  CAS  PubMed  Google Scholar 

  • Kernéis S, Caliot E, Stubbe H, Bogdanova A, Kraehenbuhl J, Pringault E (2000) Molecular studies of the intestinal mucosal barrier physiopathology using cocultures of epithelial and immune cells: a technical update. Microbes Infect 2:1119–1124

    Article  PubMed  Google Scholar 

  • Lamont AG, Adorini L (1996) IL-12: a key cytokine in immune regulation. Immunol Today 17:214–217

    Article  CAS  PubMed  Google Scholar 

  • Lightowlers MW (1996) Vaccination against cestode parasites. Int J Parasitol 26:819–824

    CAS  PubMed  Google Scholar 

  • Manetti R, Parronchi P, Giudizi MG, Piccinni MP, Maggi E, Trinchieri G, Romagnani S (1993) Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med 177:1199–1204

    CAS  PubMed  Google Scholar 

  • Mosmann TR (1991) Cytokine secretion patterns and cross-regulation of T cell subsets. Immunol Res 10:183–188

    CAS  PubMed  Google Scholar 

  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357

    CAS  PubMed  Google Scholar 

  • Palm N, Germann T, Goedert S, Hoehn P, Koelsch S, Rude E, Schmitt E (1996) Co-development of naive CD4+ cells towards T helper type 1 or T helper type 2 cells induced by a combination of IL-12 and IL-4. Immunobiology 196:475–484

    PubMed  Google Scholar 

  • Pearce EJ, Caspar P, Grzych JM, Lewis FA, Sher A (1991) Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med 173:159–166

    CAS  PubMed  Google Scholar 

  • Pond L, Wassom DL, Hayes CE (1989) Evidence for differential induction of helper T cell subsets during Trichinella spiralis infection. J Immunol 143:4232–4237

    CAS  PubMed  Google Scholar 

  • Qadir K, Metwali A, Blum AM, Li J, Elliott DE, Weinstock JV (2001) TGF-beta and IL-10 regulation of IFN-gamma produced in Th2-type schistosome granulomas requires IL-12. Am J Physiol Gastrointest Liver Physiol 281:G940–946

    CAS  PubMed  Google Scholar 

  • Smyth JD, Barrett NJ (1980) Procedures for testing the viability of human hydatid cysts following surgical removal, especially after chemotherapy. Trans R Soc Trop Med Hyg 74:649–652

    CAS  PubMed  Google Scholar 

  • Taylor MJ, Jenkins RE, Bianco AE (1996) Protective immunity induced by vaccination with Onchocerca volvulus tropomyosin in rodents. Parasite Immunol 18:219–225

    CAS  PubMed  Google Scholar 

  • Tendler M, Brito CA, Vilar MM, Serra-Freire N, Diogo CM, Almeida MS, Delbem AC, Da Silva JF, Savino W, Garratt RC, Katz N, Simpson AS (1996) A Schistosoma mansoni fatty acid-binding protein, Sm14, is the potential basis of a dual-purpose anti-helminth vaccine. Proc Natl Acad Sci U S A 93:269–273

    Article  CAS  PubMed  Google Scholar 

  • Urban JFJr, Madden KB, Svetic A, Cheever A, Trotta PP, Gause WC, Katona IM, Finkelman FD (1992) The importance of Th2 cytokines in protective immunity to nematodes. Immunol Rev 127:205–220

    CAS  PubMed  Google Scholar 

  • Vezzio N, Sarfati M, Yang LP, Demeure CE, Delespesse G (1996) Human Th2-like cell clones induce IL-12 production by dendritic cells and may express several cytokine profiles. Int Immunol 8:1963–1970

    CAS  PubMed  Google Scholar 

  • Vuitton DA (2003) The ambiguous role of immunity in echinococcosis: protection of the host or of the parasite? Acta Trop 85:119–132

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by INCO-MED (ICFP599A3PR01) –2004. We express our gratitude to A. Esteves and R. Ehrlich for providing cDNA clone EgTrp and FABP1, B. Dubois, Unity INSERM U404 for the Caco-2 cell line and J. Bienvenue for helpful discussions. The experiments comply with the current laws of the country in which they were performed.

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Authors and Affiliations

  1. Laboratory of Parasitology and Medical Mycology, Faculty of Pharmacy, Claude- Bernard University, Lyon, France

    M. Fraize, M. E. Sarciron, S. Azzouz & A. F. Petavy

  2. CGMC, UMR CNRS 5534, Claude-Bernard University, Villeurbanne, France

    D. Saboulard & G. Bosquet

  3. Immunology Laboratory, Lyon-Sud Hospital, Pierre-Bénite, France

    A. L. Debard

Authors
  1. M. Fraize
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  2. M. E. Sarciron
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  3. D. Saboulard
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  4. S. Azzouz
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  5. A. L. Debard
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  6. G. Bosquet
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  7. A. F. Petavy
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Correspondence to A. F. Petavy.

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Fraize, M., Sarciron, M.E., Saboulard, D. et al. An in vitro model to evaluate the cytokine response in Echinococcus infections. Parasitol Res 92, 506–512 (2004). https://doi.org/10.1007/s00436-004-1075-y

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  • DOI: https://doi.org/10.1007/s00436-004-1075-y

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