Hostname: page-component-8448b6f56d-m8qmq Total loading time: 0 Render date: 2024-04-16T08:24:15.326Z Has data issue: false hasContentIssue false
  • English
  • Français

In vitro induction of lymph node cell proliferation by mouse bone marrow dendritic cells following stimulation with different Echinococcus multilocularis antigens

Published online by Cambridge University Press:  13 January 2011

M.C. Margos ,
D. Grandgirard ,
S. Leib  and
Bruno Gottstein
M.C. Margos
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Bern, Laenggass-Strasse 122, CH-3012Bern, Switzerland
D. Grandgirard
Affiliation:
Institute for Infectious Diseases, University of Bern, Friedbuehlstrasse 51, CH-3010Bern, Switzerland
S. Leib
Affiliation:
Institute for Infectious Diseases, University of Bern, Friedbuehlstrasse 51, CH-3010Bern, Switzerland
Bruno Gottstein*
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Bern, Laenggass-Strasse 122, CH-3012Bern, Switzerland
*
*E-mail: bruno.gottstein@ipa.unibe.ch
Get access Rights & Permissions [Opens in a new window]

Abstract

The immune response of mice experimentally infected with Echinococcus multilocularis metacestodes becomes impaired so as to allow parasite survival and proliferation. Our study tackled the question on how different classes of E. multilocularis antigens (crude vesicular fluid (VF); purified proteinic rec-14-3-3; purified carbohydrate Em2(G11)) are involved in the maturation process of bone-marrow-derived dendritic cells (BMDCs) and subsequent exposure to lymph node (LN) cells. In our experiments, we used BMDCs cultivated from either naïve (control) or alveolar echinococcosis (AE)-infected C57BL/6 mice. We then tested surface markers (CD80, CD86, MHC class II) and cytokine expression levels (interleukin (IL)-10, IL-12p40 and tumour necrosis factor (TNF)-α) of non-stimulated BMDCs versus BMDCs stimulated with different Em-antigens or lipopolysaccharide (LPS). While LPS and rec-14-3-3-antigen were able to induce CD80, CD86 and (to a lower extent) MHC class II surface expression, Em2(G11) and, strikingly, also VF-antigen failed to do so. Similarly, LPS and rec-14-3-3 yielded elevated IL-12, TNF-α and IL-10 expression levels, while Em2(G11) and VF-antigen didn't. When naïve BMDCs were loaded with VF-antigen, they induced a strong non-specific proliferation of uncommitted LN cells. For both, BMDCs or LN cells, isolated from AE-infected mice, proliferation was abrogated. The most striking difference, revealed by comparing naïve with AE-BMDCs, was the complete inability of LPS-stimulated AE-BMDCs to activate lymphocytes from any LN cell group. Overall, the presenting activity of BMDCs from AE-infected mice seemed to trigger unresponsiveness in T cells, especially in the case of VF-antigen stimulation, thus contributing to the suppression of clonal expansion during the chronic phase of AE infection.

Type
Research Papers
Information
Journal of Helminthology , Volume 85 , Issue 2 , June 2011 , pp. 128 - 137
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Baron, R.W. & Tanner, C.E. (1976) The effect of immunosuppression on secondary Echinococcus multilocularis infections in mice. International Journal of Parasitology 6, 37–42.CrossRefGoogle ScholarPubMed
Barton, G.M. & Medzhitov, R. (2003) Toll-like receptor signaling pathways. Science 300, 1524–1525.CrossRefGoogle ScholarPubMed
Becker, T.C., Coley, S.M., Wherry, E.J. & Ahmed, R. (2005) Bone marrow is a preferred site for homeostatic proliferation of memory CD8 T cells. Journal of Immunology 174, 1269–1273.CrossRefGoogle ScholarPubMed
Bresson-Hadni, S., Vuitton, D.A., Lenys, D., Liance, M., Racadot, E. & Miguet, J.P. (1989) Cellular immune response in Echinococcus multilocularis infection in humans. I. Lymphocyte reactivity to Echinococcus antigens in patients with alveolar echinococcosis. Clinical and Experimental Immunology 78, 61–66.Google ScholarPubMed
Carter, L.L. & Dutton, R.W. (1996) Type 1 and type 2: a fundamental dichotomy for all T-cell subsets. Current Opinion in Immunology 8, 336–342.CrossRefGoogle ScholarPubMed
Caux, C., Ait-Yahia, S., Chemin, K., de Bouteiller, O., Dieu-Nosjean, M.C., Homey, B., Massacrier, C., Vanbervliet, B., Zlotnik, A. & Vicari, A. (2000) Dendritic cell biology and regulation of dendritic cell trafficking by chemokines. Springer Seminar in Immunopathology 22, 345–369.CrossRefGoogle ScholarPubMed
D'Andrea, A., Aste-Amezaga, M., Valiante, N.M., Ma, X., Kubin, M. & Trinchieri, G. (1993) Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. Journal of Experimental Medicine 178, 1041–1048.CrossRefGoogle ScholarPubMed
Dai, W.J. & Gottstein, B. (1999) Nitric oxide-mediated immunosuppression following murine Echinococcus multilocularis infection. Immunology 97, 107–116.CrossRefGoogle ScholarPubMed
Dai, W.J., Hemphill, A., Waldvogel, A., Ingold, K., Deplazes, P., Mossmann, H. & Gottstein, B. (2001) Major carbohydrate antigen of Echinococcus multilocularis induces an immunoglobulin G response independent of alphabeta+ CD4+T cells. Infection and Immunity 69, 6074–6083.CrossRefGoogle ScholarPubMed
Dai, W.J., Waldvogel, A., Siles-Lucas, M. & Gottstein, B. (2004) Echinococcus multilocularis proliferation in mice and respective parasite 14-3-3 gene expression is mainly controlled by an alphabeta CD4 T-cell-mediated immune response. Immunology 112, 481–488.CrossRefGoogle ScholarPubMed
Deplazes, P. & Gottstein, B. (1991) A monoclonal antibody against Echinococcus multilocularis Em2 antigen. Parasitology 103, 41–49.CrossRefGoogle ScholarPubMed
Dixon, J.B. (1997) Echinococcosis. Comparative Immunological and Microbiological Infectious Diseases 20, 87–94.CrossRefGoogle ScholarPubMed
Dreweck, C.M., Soboslay, P.T., Schulz-Key, H., Gottstein, B. & Kern, P. (1999) Cytokine and chemokine secretion by human peripheral blood cells in response to viable Echinococcus multilocularis metacestode vesicles. Parasite Immunology 21, 433–438.CrossRefGoogle ScholarPubMed
Emery, I., Liance, M., Deriaud, E., Vuitton, D.A., Houin, R. & Leclerc, C. (1996) Characterization of T-cell immune responses of Echinococcus multilocularis-infected C57BL/6J mice. Parasite Immunology 18, 463–472.CrossRefGoogle ScholarPubMed
Godot, V., Harraga, S., Deschaseaux, M., Bresson-Hadni, S., Gottstein, B., Emilie, D. & Vuitton, D.A. (1997) Increased basal production of interleukin-10 by peripheral blood mononuclear cells in human alveolar echinococcosis. European Cytokine Network 8, 401–408.Google ScholarPubMed
Godot, V., Harraga, S., Podoprigora, G., Liance, M., Bardonnet, K. & Vuitton, D.A. (2003) IFN alpha-2a protects mice against a helminth infection of the liver and modulates immune responses. Gastroenterology 124, 1441–1450.CrossRefGoogle ScholarPubMed
Gottstein, B. & Hemphill, A. (1997) Immunopathology of echinococcosis. Chemical Immunology 66, 177–208.Google ScholarPubMed
Gottstein, B., Deplazes, P. & Aubert, M. (1992) Echinococcus multilocularis: immunological study on the ‘Em2-positive’ laminated layer during in vitro and in vivo post-oncospheral and larval development. Parasitology Research 78, 291–297.CrossRefGoogle Scholar
Gottstein, B., Wunderlin, E. & Tanner, I. (1994) Echinococcus multilocularis: parasite-specific humoral and cellular immune response subsets in mouse strains susceptible (AKR, C57B1/6J) or ‘resistant’ (C57B1/10) to secondary alveolar echinococcosis. Clinical Experimental Immunology 96, 245–252.CrossRefGoogle Scholar
Harnett, W. & Harnett, M.M. (2008) Therapeutic immunomodulators from nematode parasites. Expert Review of Molecular Medicine 10, e18.CrossRefGoogle ScholarPubMed
Hemphill, A. & Gottstein, B. (1995) Immunology and morphology studies on the proliferation of in vitro cultivated Echinococcus multilocularis metacestodes. Parasitology Research 81, 605–614.CrossRefGoogle ScholarPubMed
Jenkins, S.J., Hewitson, J.P., Jenkins, G.R. & Mountford, A.P. (2005) Modulation of the host's immune response by schistosome larvae. Parasite Immunology 27, 385–393.CrossRefGoogle ScholarPubMed
Jenne, L., Kilwinski, J., Radloff, P., Flick, W. & Kern, P. (1998) Clinical efficacy of and immunologic alterations caused by interferon gamma therapy for alveolar echinococcosis. Clinical Infectious Diseases 26, 492–494.CrossRefGoogle ScholarPubMed
Jenne, L., Arrighi, J.F., Sauter, B. & Kern, P. (2001) Dendritic cells pulsed with unfractionated helminthic proteins to generate antiparasitic cytotoxic T lymphocyte. Parasite Immunology 23, 195–201.CrossRefGoogle ScholarPubMed
Konecny, P., Stagg, A.J., Jebbari, H., English, N., Davidson, R.N. & Knight, S.C. (1999) Murine dendritic cells internalize Leishmania major promastigotes, produce IL-12 p40 and stimulate primary T cell proliferation in vitro. European Journal of Immunology 29, 1803–1811.3.0.CO;2-F>CrossRefGoogle ScholarPubMed
Liance, M., Bresson-Hadni, S., Meyer, J.P., Houin, R. & Vuitton, D.A. (1990) Cellular immunity in experimental Echinococcus multilocularis infection. I. Sequential and comparative study of specific in vivo delayed-type hypersensitivity against E. multilocularis antigens in resistant and sensitive mice. Clinical and Experimental Immunology 82, 373–377.CrossRefGoogle ScholarPubMed
Liance, M., Bresson-Hadni, S., Vuitton, D.A., Lenys, D., Carbillet, J.P. & Houin, R. (1992) Effects of cyclosporin A on the course of murine alveolar echinococcosis and on specific cellular and humoral immune responses against Echinococcus multilocularis. International Journal of Parasitology 22, 23–28.CrossRefGoogle ScholarPubMed
Liance, M., Ricard-Blum, S., Emery, I., Houin, R. & Vuitton, D.A. (1998) Echinococcus multilocularis infection in mice: in vivo treatment with a low dose of IFN-gamma decreases metacestode growth and liver fibrogenesis. Parasite 5, 231–237.CrossRefGoogle ScholarPubMed
Lightowlers, M.W. & Rickard, M.D. (1988) Excretory-secretory products of helminth parasites: effects on host immune responses. Parasitology 96 (Suppl), S123–S166.CrossRefGoogle ScholarPubMed
Lutz, M.B., Kukutsch, N., Ogilvie, A.L., Rössner, S., Koch, F., Romani, N. & Schuler, G. (1999) An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. Journal of Immunological Methods 223, 77–92.CrossRefGoogle ScholarPubMed
Macatonia, S.E., Hosken, N.A., Litton, M., Vieira, P., Hsieh, C.S., Culpepper, J.A., Wysocka, M., Trinchieri, G., Murphy, K.M. & O'Garra, A. (1995) Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+T cells. Journal of Immunology 154, 5071–5079.CrossRefGoogle ScholarPubMed
MacDonald, A.S. & Pearce, E.J. (2002) Cutting edge: polarized Th cell response induction by transferred antigen-pulsed dendritic cells is dependent on IL-4 or IL-12 production by recipient cells. Journal of Immunology 168, 3127–3130.CrossRefGoogle ScholarPubMed
MacDonald, A.S., Straw, A.D., Bauman, B. & Pearce, E.J. (2001) CD8– dendritic cell activation status plays an integral role in influencing Th2 response development. Journal of Immunology 167, 1982–1988.CrossRefGoogle ScholarPubMed
MacDonald, A.S., Patton, E.A., La Flamme, A.C., Araujo, M.I., Huxtable, C.R., Bauman, B. & Pearce, E.J. (2002) Impaired Th2 development and increased mortality during Schistosoma mansoni infection in the absence of CD40/CD154 interaction. Journal of Immunology 168, 4643–4649.CrossRefGoogle ScholarPubMed
Maizels, R.M. & Yazdanbakhsh, M. (2003) Immune regulation by helminth parasites: cellular and molecular mechanisms. Nature Review in Immunology 3, 733–744.CrossRefGoogle ScholarPubMed
Margos, M. & Gottstein, B. (2010) Gerbu adjuvant modulates the immune response and thus the course of infection in C56BL/6 mice immunised with Echinococcus multilocularis rec14-3-3 protein. Parasitology Research 107, 623–629.CrossRefGoogle ScholarPubMed
Matsumoto, J., Müller, N., Hemphill, A., Oku, Y., Kamiya, M. & Gottstein, B. (2006) 14-3-3- and II/3-10-gene expression as molecular markers to address viability and growth activity of Echinococcus multilocularis metacestodes. Parasitology 132, 83–94.CrossRefGoogle ScholarPubMed
Mejri, N. & Gottstein, B. (2006) Intraperitoneal Echinococcus multilocularis infection in C57BL/6 mice affects CD40 and B7 costimulator expression on peritoneal macrophages and impairs peritoneal T cell activation. Parasite Immunology 28, 373–385.CrossRefGoogle ScholarPubMed
Mejri, N., Hemphill, A. & Gottstein, B. (2010) Triggering and modulation of the host–parasite interplay by Echinococcus multilocularis: a review. Parasitology 137, 557–568.CrossRefGoogle ScholarPubMed
Mellman, I. & Steinman, R.M. (2001) Dendritic cells: specialized and regulated antigen processing machines. Cell 106, 255–258.CrossRefGoogle ScholarPubMed
Meyaard, L., Hovenkamp, E., Otto, S.A. & Miedema, F. (1996) IL-12-induced IL-10 production by human T cells as a negative feedback for IL-12-induced immune responses. Journal of Immunology 156, 2776–2782.CrossRefGoogle Scholar
Mosmann, T.R. (1994) Properties and functions of interleukin-10. Advances in Immunology 56, 1–26.CrossRefGoogle ScholarPubMed
Müller, N., Frei, E., Nuñez, S. & Gottstein, B. (2007) Improved serodiagnosis of alveolar echinococcosis of humans using an in vitro-produced Echinococcus multilocularis antigen. Parasitology 134, 879–888.CrossRefGoogle Scholar
Pasare, C. & Medzhitov, R. (2004) Toll-dependent control mechanisms of CD4 T cell activation. Immunity 21, 733–741.CrossRefGoogle ScholarPubMed
Perona-Wright, G., Jenkins, S.J. & MacDonald, A.S. (2006) Dendritic cell activation and function in response to Schistosoma mansoni. International Journal of Parasitology 36, 711–721.CrossRefGoogle ScholarPubMed
Playford, M.C., Ooi, H.K., Oku, Y. & Kamiya, M. (1992) Secondary Echinococcus multilocularis infection in severe combined immunodeficient (scid) mice: biphasic growth of the larval cyst mass. International Journal of Parasitology 22, 975–982.CrossRefGoogle ScholarPubMed
Rau, M.E. & Tanner, C.E. (1975) BCG suppresses growth and metastasis of hydatid infections. Nature 256, 318–319.CrossRefGoogle ScholarPubMed
Riganò, R., Buttari, B., Profumo, E., Ortona, E., Delunardo, F., Margutti, P., Mattei, V., Teggi, A., Sorice, M. & Siracusano, A. (2007) Echinococcus granulosus antigen B impairs human dendritic cell differentiation and polarizes immature dendritic cell maturation towards a Th2 cell response. Infection and Immunity 75, 1667–1678.CrossRefGoogle ScholarPubMed
Sakaguchi, S., Yamaguchi, T., Nomura, T. & Ono, M. (2008) Regulatory T cells and immune tolerance. Cell 133, 775–787.CrossRefGoogle ScholarPubMed
Sallusto, F. & Lanzavecchia, A. (2002) The instructive role of dendritic cells on T-cell responses. Arthritis Research 4 (Suppl 3), S127–S132.CrossRefGoogle ScholarPubMed
Siles-Lucas, M. & Gottstein, B. (2003) The 14-3-3 protein: a key molecule in parasites as in other organisms. Trends in Parasitology 19, 575–581.CrossRefGoogle ScholarPubMed
Siles-Lucas, M., Felleisen, R.S., Hemphill, A., Wilson, W. & Gottstein, B. (1998) Stage-specific expression of the 14-3-3 gene in Echinococcus multilocularis. Molecular and Biochemical Parasitology 91, 281–293.CrossRefGoogle ScholarPubMed
Siles-Lucas, M., Merli, M., Mackenstedt, U. & Gottstein, B. (2003) The Echinococcus multilocularis 14-3-3 protein protects mice against primary but not secondary alveolar echinococcosis. Vaccine 21, 431–439.CrossRefGoogle Scholar
Steinman, R.M. (2003) Some interfaces of dendritic cell biology. Apmis 111, 675–697.CrossRefGoogle ScholarPubMed
Steinman, R.M. & Nussenzweig, M.C. (2002) Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proceedings of the National Academy of Sciences USA 99, 351–358.CrossRefGoogle ScholarPubMed
Stettler, M., Fink, R., Walker, M., Gottstein, B., Geary, T.G., Rossignol, J.F. & Hemphill, A. (2003) In vitro parasiticidal effect of Nitazoxanide against Echinococcus multilocularis metacestodes. Antimicrobial Agents and Chemotherapy 47, 467–474.CrossRefGoogle ScholarPubMed
Trinchieri, G. (1993) Interleukin-12 and its role in the generation of TH1 cells. Immunology Today 14, 335–338.CrossRefGoogle ScholarPubMed
Trinchieri, G. (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nature Review on Immunology 3, 133–146.CrossRefGoogle ScholarPubMed
Varol, C., Landsman, L., Fogg, D.K., Greenshtein, L., Gildor, B., Margalit, R., Kalchenko, V., Geissmann, F. & Jung, S. (2007) Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. Journal of Experimental Medicine 204, 171–180.CrossRefGoogle Scholar
Vuitton, D.A. (2003) The ambiguous role of immunity in echinococcosis: protection of the host or of the parasite? Acta Tropica 85, 119–132.CrossRefGoogle ScholarPubMed
Walker, M., Baz, A., Dematteis, S., Stettler, M., Gottstein, B., Schaller, J. & Hemphill, A. (2004) Isolation and characterization of a secretory component of Echinococcus multilocularis metacestodes potentially involved in modulating the host–parasite interface. Infection and Immunity 72, 527–536.CrossRefGoogle ScholarPubMed
Wei, X.L., Ding, J.B., Xu, Y., Wen, H. & Lin, R.Y. (2004) Change of cytokines in mice with Echinococcus multilocularis infection. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 22, 361–364(in Chinese).Google ScholarPubMed