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Abstract:

Patients with chronic Chagas' heart disease (cChHD) develop a strong IgG response against the C-terminal region of the Trypanosoma cruzi ribosomal P2β protein (TcP2β). These antibodies have been shown to exert an in vitro chronotropic effect on cardiocytes through stimulation of the β1-adrenergic receptor (β1-AR). Moreover, the presence of antibodies recognizing the TcP2β C-terminus was associated with cardiac alterations in mice immunized with the corresponding recombinant protein. Here, we demonstrate that DNA immunization could be used to modulate the specificity of the anti-TcP2β humoral response in order to avoid the production of pathogenic antibodies. After DNA injection, we detected IgG antibodies that were directed only to internal epitopes of the TcP2β molecule and that did not exert anti-β1-AR functional activity, measured as an increase in intracellular cAMP levels of transfected COS-7 cells. Accordingly, DNA-immunized mice did not present electrocardiographic alterations. These data demonstrate that anti-TcP2β antibodies elicited by DNA immunization are completely different in their specificity and functional activity from those produced during T. cruzi infection. © 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved.

Registro:

Documento: Artículo
Título:DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies
Autor:Levitus, G.; Grippo, V.; Labovsky, V.; Ghio, S.; Hontebeyrie, M.; Levin, M.J.
Filiación:Lab. Biol. Molec. Enfermedad Chagas, Inst. Invest. Ing. Genet. Biol. M., Vuelta de Obligado 2490, Buenos Aires, 1428, Argentina
Depto. Fisiol. y Biol. Molec. y Cel., Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
U. Repliement Modelisation Proteines, Dept. de Biol. Structurale et Chimie, Institut Pasteur, 28, rue du Dr Roux, 75724 Paris Cedex 15, France
Palabras clave:DNA immunization; Ribosomal P2 protein; Trypanosoma cruzi; cyclic AMP; DNA vaccine; epitope; immunoglobulin G antibody; protozoal protein; protozoon antibody; recombinant protein; ribosome protein; animal cell; animal experiment; animal model; antibody detection; antibody production; antibody specificity; article; cell strain COS7; Chagas disease; controlled study; drug effect; electrocardiography; female; genetic transfection; human; humoral immunity; immunization; mouse; nonhuman; priority journal; Trypanosoma cruzi; trypanosomiasis; Trypanosoma; Trypanosoma cruzi
Año:2003
Volumen:5
Número:15
Página de inicio:1381
Página de fin:1388
DOI: http://dx.doi.org/10.1016/j.micinf.2003.09.016
Título revista:Microbes and Infection
Título revista abreviado:Microbes Infect.
ISSN:12864579
CODEN:MCINF
CAS:cyclic AMP, 60-92-4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_12864579_v5_n15_p1381_Levitus

Referencias:

  • Chiale, P.A., Rosenbaum, M., Clinical and pharmacological characterization and treatment of potentially malignant arrhythmias of chronic chagasic cardiomiopathy (1989) Handbook of Experimental Pharmacology, 89. , E. Vaughan Williams, & T. Cambell. Berlin: Springer-Verlag
  • Kierszenbaum, F., Chagas' disease and the autoimmunity hypothesis (1999) Clin. Microbiol. Rev., 12, pp. 210-223
  • Levin, M.J., In chronic Chagas' heart disease, don't forget the parasite (1996) Parasitol. Today, 12, pp. 415-416
  • Petry, K., Eisen, H., Chagas' disease: A model for the study of autoimmune diseases (1989) Parasitol. Today, 5, pp. 111-116
  • Tarleton, R.L., Parasite persistence in the aetiology of Chagas' disease (2001) Int. J. Parasitol., 31, pp. 550-554
  • Belotti, G., In vivo detection of Trypanosoma cruzi antigens in hearts of patients with chronic Chagas' heart disease (1998) Am. Heart J., 137, p. 550
  • Brandariz, S.A., Schijman, A., Vigliano, C., Arteman, P., Viotti, R., Beldjord, C., Levin, M.J., Detection of parasite DNA in Chagas' heart disease (1995) Lancet, 346, pp. 1370-1371
  • Jones, E.M., Colley, D.G., Tostes, S., Lopes, E.R., Vnencak-Jones, C.L., Mc Curley, T.L., Amplification of Trypanosoma cruzi DNA sequences from inflammatory lesions in human chagasic cardiomyopathy (1993) Am. J. Trop. Med. Hyg., 48, pp. 348-357
  • Schijman, A., Vigliano, C., Burgos, J., Favaloro, R., Perrone, S., Laguens, R., Levin, M.J., Early diagnosis of recurrence of Trypanosoma cruzi infection by polymerase chain reaction after heart transplantation of a chronic Chagas' heart disease patient (2000) J. Heart Lung Transpl., 19, pp. 1114-1117
  • Chiale, P.A., Ferrari, I., Mahler, E., Vallazza, M.A., Elizari, M.V., Rosenbaum, M.B., Levin, M.J., Differential profile and biochemical effects of antiautonomic membrane receptor antibodies in ventricular arrhythmias and sinus node dysfunction (2001) Circulation, 103, pp. 1765-1771
  • Costa, P.C., Fortes, F.S., MacHado, A.B., Almeida, N.A., Olivares, E.L., Cabral, P.R., Pedrosa, R.C., Masuda, M.O., Sera from chronic chagasic patients depress cardiac electrogenesis and conduction (2000) Braz. J. Med. Biol. Res., 33, pp. 439-446
  • De Oliveira, S.F., Pedrosa, R.C., Nascimento, J.H., Campos De Carvalho, A.C., Masuda, M.O., Sera from chronic chagasic patients with complex cardiac arrhythmias depress electrogenesis and conduction in isolated rabbit hearts (1997) Circulation, 96, pp. 2031-2037
  • Goin, J.C., Leiros, C.P., Borda, E., Sterin-Borda, L., Interaction of human chagasic IgG with the second extracellular loop of the human heart muscarinic acetylcholine receptor: Functional and pathological implications (1997) FASEB J., 11, pp. 77-83
  • Kaplan, D., Ferrari, I., López Bergami, P., Mahler, E., Levitus, G., Chiale, P., Hoebeke, J., Levin, M.J., Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas' disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in Lupus (1997) Proc. Natl. Acad. Sci., 94, pp. 10301-10306
  • Ferrari, I., Levin, M.J., Elizari, M.V., Rosenbaum, M.B., Chiale, P.A., Cholinergic autoantibodies in sinus-node dysfunction (1997) Lancet, 350, pp. 262-263
  • Magnusson, Y., Wallukat, G., Waagstein, F., Hjalmarson, A., Hoebeke, J., Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the β1-adrenoreceptor with positive chronotropic effect (1994) Circulation, 89, pp. 2760-2767
  • Rosenbaum, M.B., Chiale, P.A., Schejtman, D., Levin, M., Elizari, M.V., Antibodies to β-adrenergic receptors disclosing agonist-like properties in idiopathic dilated cardiomyopathy and Chagas' heart disease (1994) J. Cardiovasc. Electrophysiol., 5, pp. 367-375
  • Levin, M.J., Mesri, E., Benarous, R., Levitus, G., Schijman, A., Levy-Yeyati, P., Chiale, P., Segura, E.L., Identification of major Trypanosoma cruzi antigenic determinants in chronic Chagas' heart disease (1989) Am. J. Trop. Med. Hyg., 41, pp. 530-539
  • Levitus, G., Hontebeyrie-Joskowicz, M., Van Regenmortel, M.H.V., Levin, M.J., Humoral autoimmune response to ribosomal P proteins in chronic Chagas' heart disease (1991) Clin. Exp. Immunol., 85, pp. 413-417
  • Mesri, E., Levitus, G., Hontebeyrie-Joskowicz, M., Dighiero, G., Van Regenmortel, M.H.V., Levin, M.J., Major Trypanosoma cruzi determinant in Chagas' heart disease shares homology with the systemic lupus erythematosus ribosomal P protein epitope (1990) J. Clin. Microbiol., 28, pp. 1219-1224
  • Aznar, C., López Bergami, P., Brandariz, S., Mariette, C., Liegeard, P., De Deus Alves, M.C., Luna Barreiro, E., Hontebeyrie-Joskowicz, M., Prevalence of anti-R13 antibodies in human Trypanosoma cruzi infection (1995) FEMS Immunol. Med. Microbiol., 12, pp. 231-238
  • López Bergami, P., Cabeza Meckert, P., Kaplan, D., Levitus, G., Elias, F., Quintana, F., Van Regenmortel, M.H.V., Levin, M.J., Immunization with recombinant Trypanosoma cruzi ribosomal P2β protein induces changes in the electrocardiogram of immunized mice (1997) FEMS Immunol. Med. Microbiol., 18, pp. 75-85
  • Sepulveda, P., Liegeard, P., Wallukat, G., Levin, M.J., Hontebeyrie, M., Modulation of cardiocyte functional activity by antibodies against Trypanosoma cruzi ribosomal P2 protein C-terminus (2000) Infect. Immun., 68, pp. 5114-5119
  • Gurunathan, S., Wu, C.Y., Freidag, B.L., Seder, R.A., DNA vaccines: A key for inducing long-term cellular immunity (2000) Curr. Opin. Immunol., 12, pp. 442-447
  • Mahler, E., Sepulveda, P., Jeannequin, O., Liegeard, P., Gounon, P., Wallukat, G., Eftekhari, P., Hontebeyrie, M., A monoclonal antibody against the immunodominant epitope of the ribosomal P2β protein of Trypanosoma cruzi interacts with the human β1-adrenergic receptor (2001) Eur. J. Immunol., 31, pp. 2210-2216
  • Mobini, R., Fu, R.M., Wallukat, G., Magnusson, Y., Hjalmarson, A., Hoebeke, J., A monoclonal antibody directed against an autoimmune epitope on the human β1-adrenergic receptor recognized in idiopathic dilated cardiomyopathy (2000) Hybridoma, 19, pp. 135-142
  • Schijman, A., Dusetti, N.J., Vázquez, M.P., Lafon, S., Levy-Yeyati, P., Levin, M.J., Nucleotide cDNA and complete deduced amino acid sequence of a Trypanosoma cruzi ribosomal P protein (P-JL5) (1990) Nucleic Acids Res., 18, p. 3399
  • Kozak, M., The scanning model for translation: An update (1989) J. Cell Biol., 108, pp. 229-241
  • Spinella, S., Liegeard, P., Hontebeyrie-Joskowicz, M., Trypanosoma cruzi: Predominance of IgG2a in nonspecific humoral response during experimental Chagas' disease (1992) Exp. Parasitol., 74, pp. 46-56
  • Sin, J.I., Kim, J.J., Ugen, K.E., Ciccarelli, R.B., Higgins, T.J., Weiner, D.B., Enhancement of protective humoral (Th2) and cell-mediated (Th1) immune responses against herpes simplex virus-2 through co-delivery of granulocyte-macrophage colony-stimulating factor expression cassettes (1998) Eur. J. Immunol., 28, pp. 3530-3540
  • Weiss, W.R., Ishii, K.J., Hedstrom, R.C., Sedegah, M., Ichino, M., Barnhart, K., Klinman, D.M., Hoffman, S.L., A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccine (1998) J. Immunol., 161, pp. 2325-2332
  • Leclerc, C., Deriaud, E., Rojas, M., Whalen, R.G., The preferential induction of a Th1 immune response by DNA-based immunization is mediated by the immunostimulatory effect of plasmid DNA (1997) Cell Immunol., 179, pp. 97-106
  • Peng, H.J., Su, S.N., Chang, Z.N., Chao, P.L., Kuo, S.W., Tsai, L.C., Induction of specific Th1 responses and suppression of IgE antibody formation by vaccination with plasmid DNA encoding der f 11 (2002) Vaccine, 20, pp. 1761-1768
  • Sharma, A.K., Khuller, G.K., DNA vaccines: Future strategies and relevance to intracellular pathogens (2001) Immunol. Cell Biol., 79, pp. 537-546
  • Watts, A.M., Kennedy, R.C., DNA vaccination strategies against infectious diseases (1999) Int. J. Parasitol., 29, pp. 149-163
  • Doe, B., Selby, M., Barnett, S., Baenziger, J., Walker, C.M., Induction of cytotoxic T lymphocytes by intramuscular immunization with plasmid DNA is facilitated by bone marrow-derived cells (1996) Proc. Natl. Acad. Sci. USA, 93, pp. 8578-8583
  • Reina-San-Martin, B., Cosson, A., Minoprio, P., Lymphocyte polyclonal activation: A pitfall for vaccine design against infectious agents (2000) Parasitol. Today, 16, pp. 62-67
  • Minoprio, P., Burlen, O., Pereira, P., Guilbert, B., Andrade, L., Hontebeyrie-Joskowicz, M., Coutinho, A., Most B cells in acute Trypanosoma cruzi infection lack parasite specificity (1988) Scand. J. Immunol., 28, pp. 553-561
  • Brener, Z., Krettli, A.U., (1990) Immunology of chagas'Disease, Modern Parasite Biology, pp. 247-261. , Wiler D.J. New York, NY: W.H. Freeman & Co
  • La Flamme, A.C., Kahn, S.J., Rudensky, A.Y., Van Voorhis, W.C., Trypanosoma cruzi-infected macrophages are defective in major histocompatibility complex class II antigen presentation (1997) Eur. J. Immunol., 27, pp. 3085-3094
  • Garcia, F., Sepulveda, P., Liegeard, P., Gregoire, J., Hermann, E., Lemonnier, F., Langlade-Demoyen, P., Lone, Y.C., Identification of HLA-A*0201-restricted cytotoxic T-cell epitopes of Trypanosoma cruzi TcP2β protein in HLA-transgenic mice and patients (2003) Microbes Infect., 5, pp. 351-359

Citas:

---------- APA ----------
Levitus, G., Grippo, V., Labovsky, V., Ghio, S., Hontebeyrie, M. & Levin, M.J. (2003) . DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies. Microbes and Infection, 5(15), 1381-1388.
http://dx.doi.org/10.1016/j.micinf.2003.09.016
---------- CHICAGO ----------
Levitus, G., Grippo, V., Labovsky, V., Ghio, S., Hontebeyrie, M., Levin, M.J. "DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies" . Microbes and Infection 5, no. 15 (2003) : 1381-1388.
http://dx.doi.org/10.1016/j.micinf.2003.09.016
---------- MLA ----------
Levitus, G., Grippo, V., Labovsky, V., Ghio, S., Hontebeyrie, M., Levin, M.J. "DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies" . Microbes and Infection, vol. 5, no. 15, 2003, pp. 1381-1388.
http://dx.doi.org/10.1016/j.micinf.2003.09.016
---------- VANCOUVER ----------
Levitus, G., Grippo, V., Labovsky, V., Ghio, S., Hontebeyrie, M., Levin, M.J. DNA immunization with the ribosomal P2β gene of Trypanosoma cruzi fails to induce pathogenic antibodies. Microbes Infect. 2003;5(15):1381-1388.
http://dx.doi.org/10.1016/j.micinf.2003.09.016