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Abstract:

Trypanosoma cruzi, the agent of Chagas disease contains a major cysteine proteinase, cruzipain (Cz), with an unusual carboxyl-terminal extension (C-T). We have previously reported the presence of sulfate groups in the N-linked oligosaccharide chains of this domain. In order to evaluate the immune responses to sulfated moieties on Cz, BALB/c mice were immunized with purified Cz and C-T prior and after desulfation treatment. The humoral immune response to sulfates on Cz or C-T was mainly IgG2b. Interestingly, the abolishment of IgG2b reactivity when desulfated antigens were used as immunogens demonstrates that esterified sulfate groups are absolutely required for eliciting IgG2b response to Cz. Sera from chronically T. cruzi -infected subjects with mild disease displayed higher levels of total IgG and IgG2 antibodies specific for sulfated epitopes compared with those in more severe forms of the disease. A significant reduction of C-T-specific delayed-type hypersensitivity reaction in C-T-immunized mice was observed when desulfated C-T was challenged, suggesting the involvement of sulfate groups in the generation of memory T-cell responses. Moreover, immunization with C-T in the absence of infection elicited ultrastructural abnormalities in heart tissue. Surprisingly, hearts from sulfate-depleted C-T-immunized mice did not present pathological alterations. This is the first report showing that sulfate-bearing glycoproteins from trypanosomatids are able to elicit specific humoral and cellular immune responses and appeared to be involved in the generation of heart tissue damage. These results represent a further step in the understanding of the role of Cz in the course of T. cruzi infection. © The Japanese Society for Immunology. 2008. All rights reserved.

Registro:

Documento: Artículo
Título:Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice
Autor:Acosta, D.M.; Arnaiz, M.R.; Esteva, M.I.; Barboza, M.; Stivale, D.; Orlando, U.D.; Torres, S.; Laucella, S.A.; Couto, A.S.; Duschak, V.G.
Filiación:Departamento de Investigación, Instituto Nacional de Parasitología 'Dr Mario Fatala Chaben', ANLIS-Malbrán, Argentina Av. Paseo Colón 568, Buenos Aires 1063, Argentina
Departamento de Bioestadística, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1428, Argentina
Hospital Interzonal General de Agudos 'Eva Perón' San Martín, Provincia de Buenos Aires, Argentina
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina
Palabras clave:C-T domain; Cruzipain; Glycoprotein; Sulfated epitopes; Trypanosoma cruzi; antigen; cruzipain; epitope; immunoglobulin G antibody; immunoglobulin G2b; sulfate; animal experiment; animal model; animal tissue; article; Bagg albino mouse; carboxy terminal sequence; cellular immunity; controlled study; delayed hypersensitivity; disease course; disease severity; enzyme activity; female; heart injury; humoral immunity; immunization; immunopathogenesis; immunoreactivity; memory T lymphocyte; mouse; nonhuman; parasitosis; priority journal; protein domain; protein targeting; serology; Trypanosoma cruzi; Animals; Chagas Disease; Chronic Disease; Cysteine Endopeptidases; Disease Models, Animal; Female; Heart Diseases; Humans; Hypersensitivity, Delayed; Immunoglobulin G; Injections, Subcutaneous; Mice; Mice, Inbred BALB C; Myocardium; Peptide Fragments; Protein Structure, Tertiary; Reproducibility of Results; Serologic Tests; Sulfates; Trypanosoma cruzi
Año:2008
Volumen:20
Número:4
Página de inicio:461
Página de fin:470
DOI: http://dx.doi.org/10.1093/intimm/dxm149
Título revista:International Immunology
Título revista abreviado:Int. Immunol.
ISSN:09538178
CODEN:INIME
CAS:sulfate, 14808-79-8; cruzipain, EC 3.4.22.-; Cysteine Endopeptidases, EC 3.4.22.-; Immunoglobulin G; Peptide Fragments; Sulfates
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_09538178_v20_n4_p461_Acosta.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09538178_v20_n4_p461_Acosta

Referencias:

  • World Bank/World Health Organization 2002. UNDP/World Bank/WHO special programme for research and training in tropical diseases control of Chagas disease. Report of a WHO Expert Committee World Health Program. Tech. Rep. Ser. 905:1; Pan American Health Organization 1984. Status of Chagas disease in the region of Americas. Epidemiol. Bull. 5; Cazzulo, J.J., Stoka, V., Turk, V., The major cysteine proteinase of Trypanosoma cruzi: A valid target for chemotherapy of Chagas disease (2001) Curr. Pharm. Des, 7, p. 1143
  • Coombs, G.H., Mottram, J.C., Proteinases of trypanosomes and Leishmania (1997) Trypanosomiasis and Leishmaniasis, p. 177. , Hide, G, Mottram, J. C, Coombs, G. H. and Holmes, P. H, eds, CAB International, Oxford
  • Sharfstein, J., Schechter, M., Senna, M., Peralta, J.M., Mendonca-Previato, L., Miles, M.M., Trypanosoma cruzi: Characterization and isolation of a 57/51,000 m.w. surface glycoprotein (GP57/51) expressed by epimastigotes and blood-stream trypomastigotes (1986) J. Immunol, 137, p. 1336
  • Martinez, J., Campetella, O., Frasch, A.C.C., Cazzulo, J.J., The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is antigenic in human infections (1991) Infect. Immun, 59, p. 4275
  • Martinez, J., Campetella, O., Frasch, A.C.C., Cazzulo, J.J., The reactivity of sera from chagasic patients against different fragments of cruzipain, the major cysteine proteinase from Trypanosoma cruzi, suggests the presence of defined antigenic and catalytic domains (1993) Immunol. Lett, 35, p. 191
  • Souto-Padron, T., Campetella, O., Cazzulo, J.J., De Souza, W., Cysteine proteinases in T. cruzi immunocytochemical localization and involvement in parasite-host cell interaction (1990) J. Cell Sci, 96, p. 485
  • Parussini, F., Duschak, V.G., Cazzulo, J.J., Membrane bound cysteine proteinase isoforms in different developmental stages of Trypanosoma cruzi (1998) Cell. Mol. Biol, 44, p. 513
  • Duschak, V.G., Barboza, M., Couto, A.S., Trypanosoma cruzi partial characterization of minor cruzipain isoforms non-adsorbed to Concanavalin A-Sepharose (2003) Exp. Parasitol, 104, p. 122
  • Yokoyama-Yasunaka, J.K.U., Pral, E.M.F., Oliveira, O.C., Alfieri, S.C., Stolf, A.M.S., Trypanosoma cruzi: Identification of proteinases in shed components of trypomastigote forms (1994) Acta Trop, 57, p. 307
  • Duschak, V.G., Barboza, M., Garcia, G.A., Lammel, E.M., Couto, A.S., Isola, E.L., Novel cysteine proteinase in Trypanosoma cruzi metacyclogenesis (2006) Parasitology, 132, p. 345
  • Giordanengo, L., Maldonado, C., Rivarola, H.W., Induction of antibodies reactive to cardiac myosin and development of heart alterations in cruzipain-immunized mice and their offspring (2000) Eur. J. Immunol, 30, p. 3181
  • Schnapp, A.R., Eickhoff, C.S., Sizemore, D., Curtiss, R., Hoft, D.F., Cruzipain induces both mucosal and systemic protection against Trypanosoma cruzi in mice (2002) Infect. Immun, 70, p. 5065
  • Arnholdt, A.C.V., Piuvezam, M.R., Russo, D.M., Analysis and partial epitope mapping of human T cell responses to Trypanosoma cruzi cysteinyl proteinase (1993) J. Immunol, 151, p. 3171
  • Murta, A.C., Leme, V.C., Milani, S.R., Travassos, L.R., Scharfatein, J., Glycoprotein GP57/51 of Trypanosoma cruzi: Structural and conformational epitopes defined with monoclonal antibodies (1988) Mem. Inst. Oswaldo Cruz, 83 (SUPPL. 1), p. 419
  • Morrot, A., Strickland, D. K., Higuchi, M.de M. L., Reis, M., Pedrosa, R. and Scharfstein, J. 1997. Human T cell responses against the major cysteine proteinase (cruzipain) of Trypanosoma cruzi: Role of the multifunctional alpha 2-macroglobulin receptor in antigen presentation by monocytes. Int. Immunol. 9:825; Giordanengo, L., Guiñazú, N., Stempin, C., Fretes, R., Cerbán, F., Gea, S., Cruzipain, a major Trypanosoma cruzi antigen, conditions the host immune response in favour of the parasite (2002) Eur. J. Immunol, 32, p. 1003
  • Duschak, V.G., Riarte, A., Segura, E.L., Laucella, S.A., Humoral immune response to cruzipain and cardiac dysfunction in chronic Chagas disease (2001) Immunol. Lett, 78, p. 135
  • Petry, K., Nudelman, E., Eisen, H., Hakomori, S., Sulfated lipids represent common antigens on the surface of Trypanosoma cruzi and mammalian tissues (1988) Mol. Biochem. Parasitol, 30, p. 113
  • Uhrig, M.L., Couto, A.S., Zingales, B., Colli, W., Lederkremer, R.M., Metabolic labelling and partial characterization of a sulfoglycolipid in Trypanosoma cruzi trypomastigotes (1992) Carbohydr. Res, 231, p. 329
  • Barboza, M., Duschak, V.G., Fukuyama, Y., Structural analysis of the N-glycans present in cruzipain, the major cysteine proteinase of Trypanosoma cruzi. Identification of sulfated high-mannose type oligosaccharides (2005) FEBS J, 272, p. 3803
  • Wynne de Martini, G.J., Abramo Orrego, L., de Rissio, A.M., Alvarez, M., Mujica, L.P., Cultivo de Trypanosoma cruzi en un medio monofásico. (1980) Medicina (B Aires), 40, p. 109
  • Labriola, C., Souza, M., Cazzulo, J.J., Purification of the major cysteine proteinase (cruzipain) from Trypanosoma cruzi by affinity chromatography (1993) Biol. Res, 26, p. 101
  • Parussini, F., Garcia, M., Mucci, J., Characterization of a lysosomal serinecarboxypeptidase from Trypanosoma cruzi (2003) Mol. Biochem. Parasitol, 131, p. 11
  • Barboza, M., Duschak, V.G., Cazzulo, J.J., Lederkremer, R.M., Couto, A.S., Presence of sialic acid in N-linked oligosaccharide chains and O-linked N-acetylglucosamine in cruzipain, the major cysteine proteinase of Trypanosoma cruzi (2003) Mol. Biochem. Parasitol, 27, p. 69
  • Freeze, H.H., Yeh, R., Miller, A.L., Kornfeld, S., Structural analysis of the asparagine-linked oligosaccharides from free lysosomal enzymes of Dictyostelium discoideum (1983) J. Biol. Chem, 258, p. 14874
  • World Health Organization Control of Chagas disease. Report of a WHO Expert Committee World Health Program. Tech. Rep. Ser. 811:1; Kuschnir, E., Sgammini, H., Castro, R., Evequoz, C., Ledesma, R., Brunetto, J., Evaluation of cardiac function by radioisotopic angiography, in patients with chronic Chagas cardiopathy (1985) Arq. Bras. Cardiol, 45, p. 249
  • Laemmli, U.K., Cleavage of structural proteins during the assembly of the head of bacteriophage T4 (1970) Nature, 227, p. 680
  • Oakley, B.R., Kirsch, D.R., Morris, R., A simplified ultrasensitive silver stain for detecting proteins in polyacrylamide gels (1980) Anal. Biochem, 105, p. 361
  • Duschak, V.G., Ciaccio, M., Nasser, J.R., Basombrío, M.A., Enzymatic activity, protein expression and gene sequence of cruzipain in virulent and attenuated Trypanosoma cruzi strains (2001) J. Parasitol, 87, p. 1016
  • Bradford, J., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal. Biochem, 72, p. 248
  • Del Nery, E., Juliano, M.A., Lima, A.P.C.A., Scharfstein, J., Juliano, L., Kininogenase activity by the major cysteinyl proteinase (cruzipain) from Trypanosoma cruzi (1997) J. Biol. Chem, 272, p. 25713
  • Scharfstein, J., Morrot, A., A role for extracellular amastigotes in the immunopathology of Chagas disease (1999) Mem. Inst. Oswaldo Cruz, 94, p. 51
  • Laderach, D., Cerbán, F., Motran, C., Vottero de Cima, E., Gea, S., Trypanosoma cruzi: The major cysteinyl proteinase (cruzipain) is a relevant immunogen of parasite acidic antigens (FIII) (1996) Int. J. Parasitol, 26, p. 1249
  • Pedrosa, R.C., Saad, E.A., Scharfstein, J., Lima, A.M., The proliferative response of T cells against cruzipain in chronic chagasic cardiopathy (1996) Rev. Soc. Bras. Med. Trop, 29, p. 331
  • Klemba, M., Goldberg, D.E., Biological roles of proteases in parasitic protozoa (2002) Annu. Rev. Biochem, 71, p. 275
  • McKerrow, J.H., Mc Grath, M.E., Engel, J.C., The cysteine protease of Trypanosoma cruzi as a model for antiparasite drug design (1995) Parasitol. Today, 11, p. 279
  • Duschak, V.G., Couto, A.S., An insight on targets and patented drugs for chemotherapy of Chagas disease. A Review (2007) Recent Patents Ant-Infect. Drug Discov, 2, p. 19
  • Bernstein, H.B., Compans, R.W., Sulfation of the human immunodeficiency virus envelope glycoprotein (1992) J. Virol, 66, p. 6953
  • Kawasaki, N., Haishima, Y., Ohta, M., Structural analysis of sulfated N-linked oligosaccharides in erythropoietin (2001) Glycobiology, 11, p. 1043
  • Van Rooijen, J.J., Kamerling, J.P., Vliegenthart, J.F., Sulfated di-, tri-and tetra-antennary N-glycans in human Tamm-Horsfall glycoprotein (1998) Eur. J. Biochem, 256, p. 471
  • Noguchi, N., Nakano, M., Structure of the acidic N-linked carbohydrate chains of the 55-kDa glycoprotein family (PZP3) from porcine zona pellucida (1992) Eur. J. Biochem, 213, p. 39
  • Kawasaki, N., Ohta, M., Hyuga, S., Hashimoto, O., Hayakawa, T., Application of liquid chromatography/mass spectrometry and liquid chromatography with tandem mass spectrometry to the analysis of the site-specific carbohydrate heterogeneity in erythropoietin (2000) Anal. Biochem, 285, p. 82
  • Honke, K., Taniguchi, N., Sulfotransferases and sulfated oligosaccharides (2002) Med. Res. Rev, 22, p. 637
  • Freeze, H.H., Wolgast, D., Structural analysis of the N-linked oligosaccharides glycoproteins secreted by Dictyostelium discoideum Identification of mannose-6-sulfate (1986) J. Biol. Chem, 261, p. 127
  • Brodskyn, C., Silva, A., Takehara, H., Mota, I., IgG subclasses responsible for immune clearance in mice infected with Trypanosoma cruzi (1989) Immunol. Cell Biol, 67, p. 343
  • Rowland, E.C., Mikhail, K.S., McCormick, T.S., Isotype determination of anti-Trypanosoma cruzi antibody in murine Chagas' disease (1992) J. Parasitol, 78, p. 557
  • Cordeiro Drumond, F., Assis, O., Da Costa, M.O., Jorge, S., Correa-Oliveira, R., Romanha, A.J., Anti-Trypanosoma cruzi immunoglobulin G1 can be useful tool for diagnosis and Prognosis of human Chagas' disease (2001) Clin. Diagn. Lab. Immunol, 8, p. 112
  • Fiorentino, B.F., Bond, M.W., Mosmann, T.R., Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones (1989) J. Exp. Med, 170, p. 2081
  • Hoft, D.F., Lynch, R.G., Kirchhoff, L.V., Kinetic analysis of antigen-specific immune responses in resistant and susceptible mice during infection with Trypanosoma cruzi (1993) J. Immunol, 151, p. 7038
  • Jankovic, D., Zhugong, L., Gause, W.C., Th1 and Th2-cell commitment during infectious disease: Asymmetry in divergent pathways (2001) Trends Immunol, 22, p. 450
  • Laucella, S.A., Postam, M., Martin, D., Frequency of interferon- gamma-producing T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas disease (2004) J. Infect. Dis, 189, p. 909
  • Albareda, M.C., Laucella, S.A., Alvarez, M.G., Trypanosoma cruzi modulates the profile of memory CD8+ T cells in chronic Chagas' disease patients (2006) Int. Immunol, 18, p. 465
  • Schmitz, J., Kuroda, M.J., Santra, S., Effect of humoral immune responses on controlling viremia during primary infection of rhesus monkeys with simian immunodeficiency virus (2003) J. Virol, 77, p. 2165
  • Aucan, C., Traore, Y., Tall, F., High immunoglobulin G2 (IgG2) and low IgG4 levels are associated with human resistance to Plasmodium falciparum malaria (2000) Infect. Immun, 68, p. 1252
  • Muller, I., Kropf, P., Etges, R.J., Louis, J.A., Gamma interferon response in secondary Leishmania major infection: Role of CD8+ T cells (1993) Infect. Immun, 61, p. 3730
  • Bunce, C., Bell, E.B., CD45RC isoforms define two types of CD4 memory T cells, one of which depends on persisting antigen (1997) J. Exp. Med, 185, p. 767
  • Black, C.A., Delayed type hypersensitivity, current theories with an historic perspective (1999) Dermatol. Online J, 5, p. 7
  • Liu, Y., Misulovin, Z., Bjorkman, P.J., The molecular mechanism of sulfated carbohydrate recognition by the cysteine-rich domain of mannose receptor (2001) J. Mol. Biol, 305, p. 481
  • Linehan, S.A., The mannose receptor is expressed by subsets of APC in non-lymphoid organs (2005) BMC Immunol, 6, p. 4

Citas:

---------- APA ----------
Acosta, D.M., Arnaiz, M.R., Esteva, M.I., Barboza, M., Stivale, D., Orlando, U.D., Torres, S.,..., Duschak, V.G. (2008) . Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice. International Immunology, 20(4), 461-470.
http://dx.doi.org/10.1093/intimm/dxm149
---------- CHICAGO ----------
Acosta, D.M., Arnaiz, M.R., Esteva, M.I., Barboza, M., Stivale, D., Orlando, U.D., et al. "Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice" . International Immunology 20, no. 4 (2008) : 461-470.
http://dx.doi.org/10.1093/intimm/dxm149
---------- MLA ----------
Acosta, D.M., Arnaiz, M.R., Esteva, M.I., Barboza, M., Stivale, D., Orlando, U.D., et al. "Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice" . International Immunology, vol. 20, no. 4, 2008, pp. 461-470.
http://dx.doi.org/10.1093/intimm/dxm149
---------- VANCOUVER ----------
Acosta, D.M., Arnaiz, M.R., Esteva, M.I., Barboza, M., Stivale, D., Orlando, U.D., et al. Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice. Int. Immunol. 2008;20(4):461-470.
http://dx.doi.org/10.1093/intimm/dxm149