Immune response in mice immunized with acidic antigenic fractions from Trypanosoma cruzi cytosol

Gea, Susana; Gruppi, Adriana; Cerban, Fabio; Pistoresi Palencia, Maria C.; Vottero-Cima, Elsa

doi:10.1590/S0036-46651992000500003

Abstracts

The humoral and cellular immune responses as well as the resistance to infection with bloodstream forms of T. cruzi were studied in mice immunized with acidic antigenic fractions from parasite cytosol, F III and F IV, plus Bordetella pertussis as adjuvant. The immunization with F III induced positive ITH and DTH responses to homologous antigens. In mice immunized with F IV, the ITH was negative and four out of six animals presented positive DTH reactions. In both groups of mice the analysis of IgG aginst T. cruzi showed that the major isotype elicited was IgG1. Specific IgE was also detected in sera from F III immunized mice, thus confirming the presence of homocytothropic antibodies. The parasitemias reached by F III and F IV immunized mice after challenge were lower than those of the controls showing in this way a partial protection against the acute infection. The histological studies of heart and skeletal muscle performed two months after the infection revealed variable mononuclear infiltration in all infected mice despite immunization.

Trypanosoma cruzi; Immune response; Acidic antigens

As respostas humorais e celulares, assim como a resistência à infecção a formas sanguícolas do T. cruzi foram estudadas em camundongos imunizados com as frações antigênicas ácidas do Citosol parasitário, F III e F IV com Bordetella pertussis como adjuvante. A imunização com F III induziu respostas positivas ITH e DTH aos antígenos homólogos. Em camundongos imunizados com F IV o ITH foi negativo e quatro dos seis animais apresentaram reações DTH positivas. Em ambos os grupos de camundongos a análise de IgG contra T. cruzi mostrou que o principal isotipo produzido foi IgG1. IgE específico foi também detectado em soros de camundongos imunizados com F III, portanto confirmando a presença de anticorpos homocitotrópicos. As parasitemias atingidas pelos camundongos imunizados por F III e F IV após desafio foram mais baixas do que aquelas dos controles mostrando proteção parcial contra a infecção aguda. Os estudos histológicos do coração e do músculo esquelético realizados dois meses depois da infecção revelaram infiltrado mononuclear de intensidade variável em todos os camundongos infectados a despeito da imunização.

ORIGINAL ARTICLES

Immune response in mice immunized with acidic antigenic fractions from Trypanosoma cruzi cytosol

Resposta imune em camundongos imunizados com a fração ácida antigênica do Citosol do Trypanosoma cruzi

Susana Gea; Adriana Gruppi; Fabio Cerban; Maria C. Pistoresi Palencia; Elsa Vottero-Cima

Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Argentina

^{Address for correspondence} Address for correspondence: Susana Gea Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Ciudad Universitária Sucursal 16 C.C. 61. 5016. Córdoba. Argentina

SUMMARY

The humoral and cellular immune responses as well as the resistance to infection with bloodstream forms of T. cruzi were studied in mice immunized with acidic antigenic fractions from parasite cytosol, F III and F IV, plus Bordetella pertussis as adjuvant. The immunization with F III induced positive ITH and DTH responses to homologous antigens. In mice immunized with F IV, the ITH was negative and four out of six animals presented positive DTH reactions. In both groups of mice the analysis of IgG aginst T. cruzi showed that the major isotype elicited was IgG1. Specific IgE was also detected in sera from F III immunized mice, thus confirming the presence of homocytothropic antibodies. The parasitemias reached by F III and F IV immunized mice after challenge were lower than those of the controls showing in this way a partial protection against the acute infection. The histological studies of heart and skeletal muscle performed two months after the infection revealed variable mononuclear infiltration in all infected mice despite immunization.

Key words: Trypanosoma cruzi; Immune response; Acidic antigens.

RESUMO

As respostas humorais e celulares, assim como a resistência à infecção a formas sanguícolas do T. cruzi foram estudadas em camundongos imunizados com as frações antigênicas ácidas do Citosol parasitário, F III e F IV com Bordetella pertussis como adjuvante. A imunização com F III induziu respostas positivas ITH e DTH aos antígenos homólogos. Em camundongos imunizados com F IV o ITH foi negativo e quatro dos seis animais apresentaram reações DTH positivas. Em ambos os grupos de camundongos a análise de IgG contra T. cruzi mostrou que o principal isotipo produzido foi IgG1. IgE específico foi também detectado em soros de camundongos imunizados com F III, portanto confirmando a presença de anticorpos homocitotrópicos. As parasitemias atingidas pelos camundongos imunizados por F III e F IV após desafio foram mais baixas do que aquelas dos controles mostrando proteção parcial contra a infecção aguda. Os estudos histológicos do coração e do músculo esquelético realizados dois meses depois da infecção revelaram infiltrado mononuclear de intensidade variável em todos os camundongos infectados a despeito da imunização.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

ACKNOWLEDGEMENTS

We thank Dr. E. Hliba for his advice with the histological studies. This work was supported by the Secretaria de Ciencia y Técnica, Ministerio de Educación y Justicia (SECYT) and the Consejo de Investigaciones Científicas y Tecnologicas de la Província de Cordoba (CONICOR), ARGENTINA.

RERERENCIAS

1. ARAUJO, F.G. - Development of resistance to Trypanosoma cruzi in mice depends on a viable population of L₃T₄(CD₄) T lymphocytes. Infect. Immun., 57: 2246-2248, 1989.

2. BASSO, B.; MORETTI, E.R.A. & DOMINGUEZ, M. - Cultivo de Trypanosoma cruzi en medio monofasico con aireacion para la obtención de antigenos. Medicina (B. Aires), 40: 428-432, 1980.

3. BRODSKYN, C.I.; SILVA, A.M.M. da; TAKEHARA, H.A. & MOTA, I. - Characterization of antibody isotype responsible for immune clearance in mice infected with T. cruzi. Immunol. Lett., 18: 255-258, 1988.

4. BRODSKYN, C.I.; SILVA, A.M.M. da; TAKEHARA, H.A. & MOTA I. - IgG subclasses responsible for immune clearance in mice infected with Trypanosoma cruzi. Immunol. Cell Biol., 67: 343-348, 1989.

5. GEA, S.; EVEQUOZ, C.; RODRIGUEZ, P. & VOTTERO-CIMA, E. - Detection of T. cruzi antigens reactive with IgG antibodies from patients with chronic Chagas disease. Medicina (B. Aires), 40: 121, 1980.

6. GEA, S.; RODRIGUEZ, P. & VOTTERO-CIMA, E. - Characterization of Trypanosoma cruzi antigens recognized by sera from patients with chronic Chagas disease. Int. Arch. Allergy, 84: 410-413, 1987.

7. GEA, S.; GRUPPI, A.; BASSO, B.; MENSO, E. & VOTTERO-CIMA, E. - Antibodies to T. cruzi cytosol acidic antigens (F IV) in Chagas disease recognize parasite cell surface and human heart epitopes. J. clin. lab. Immunol. (in press).

8. GRUPPI, A.; MORETTI, E.R.A.; BASSO, B. & VOTTERO-CIMA, E. - Exoantigenos del Trypanosoma cruzi. Epitopes reactivos con inmunoglobulinas de pacientes con enfermedad de Chagas. Medicina (B. Aires), 48: 161, 1988.

9. HEINZEL, F.P.; SADICK, M.D.; HOLADAY, B.J.; COFFMAN, R.L. & LOCKSLEY, R.M. - Reciprocal expression of interferon Y or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J. exp. Med., 169: 59-72, 1989.

10. HONTEBEYRIE-JOSKOWICZ, M.; SAID, G.; MILON, G.; MARCHAL, G. & EISEN, H. - L3T4 T cells able to mediate parasite-specific delayed-type hypersensitivity play a role in the pathology of experimental Chagas disease. Europ. J. Immunol., 17: 1027-1033, 1987.

11. IOSA, D.; DE QUATTRO, V.; DE PING LEE, D.; ELKAYAM, U. & PALMERO, H. - Plasma norepineph-rine in Chagas cardioneuromyopathy a marker of progressive dysautonomia. Amer. Heart J., 117: 882-887 1989.

12. KRETTLI, A.U. & BRENER, Z. - Resistance against T. cruzi associated to anti-living trypomastigotes antibodies. J. Immunol., 128: 2009-2012, 1982.

13. MOTA, I. & UMEKITA, L.F. - The effect C3 depletion on the clearance of T. cruzi induced by IgG antibodies. Immunol. Lett., 21: 221-225, 1989.

14. REED, S. - In vivo administration of recombinant INF-gamma induce macrophage activation, and prevents acute disease, immune supression and death in experimental T. cruzi infection. J. Immunol., 140: 4342-4347, 1988.

15. RIBEIRO dos SANTOS, R.; PIRMEZ, C. & SAVINO, W. - Rol of autoreactive immunological mechanisms in chagasic carditis. Res. Immunol., 142: 134-137, 1991

16. RIBEIRO dos SANTOS, R.; ROSSI, M.A.; LAUS, J.L.; SILVA, J.S.; SAVINO, W. & MENGEL, J.O. - And CD4 abrogates rejection and restablishes long term tolerance to singeneic newborn hearts grafted in mice chronically infected with Trypanosoma cruzi. J. exp. Med., (in press) 1991.

17. ROTEMBERG, M.E.; CARDONI, R.L.; DE TITTO, E.H.; MORENO, M. & SEGURA, E.L. - Trypanosoma cruzi: immune response in mice immunized with parasite antigens. Exp. Parasit., 65: 101-108, 1988.

18. TAKEHARA, H.A.; CARDOSO, D.F.; SILVA, A.M. da MOTA, J. - Lytic antibodies elicited by Trypanosoma cruzi infection recognize epitopes present on both bloodstream trypomastigote and epimastigote forms of parasite. Rev. Inst. Med. trop. S. Paulo, 30: 351-356, 1988.

19. TAMBOURGY, D.V.; KIPNIS, T.L. & DIAS DA SILVA, W. - Trypanosoma cruzi: antibody dependent killing of bloodstream trypomastigotes by mouse bone marrow-derivated mast cells and by mastocytoma cells. Exp. Parasit., 68: 192-201, 1989.

20. TRISCHMAN, T.; TANOWITZ, H.; WITTNER, M. & BLOOM, B. - Trypanosoma cruzi: role of immune response in the natural resistance of imbred strain of mice. Exp. Parasit., 45: 160-168, 1978.

21. UMEKITA, L.F.; TAKEHARA, H.A. & MOTA, I. - Role of the antibody Fc in the immune clearance of Trypanosoma cruzi. Immunol. Lett., 17: 85-89, 1988.

22. VIGNALI, D.A.A.; BICKLE, Q.D. & TAYLOR, M.C. - Immunity to Schistosoma mansoni in vivo. Contradiction or clarification? Immunol. Today, 10: 410-416, 1989.

23. VOLLER, A.; BIDWELL, D.N. & BARTLETT, A. - Dynatech Laboratories. Alexandria V. A., 1979.

24. VOTTERO-CIMA, E.; FAILLACI, G.; RUBIOLO, E.; GEA, S. & PISTORESI, M.C. - Heterogeneidad de la respuesta inmune humoral en humanos infectados con T. cruzi. Medicina (B. Aires),40: 121, 1980.

Recebido para publicação em 14/1/1991

Aceito para publicação em 28/4/1992

1. ARAUJO, F.G. - Development of resistance to Trypanosoma cruzi in mice depends on a viable population of L₃T₄(CD₄) T lymphocytes. Infect. Immun., 57: 2246-2248, 1989.
2. BASSO, B.; MORETTI, E.R.A. & DOMINGUEZ, M. - Cultivo de Trypanosoma cruzi en medio monofasico con aireacion para la obtención de antigenos. Medicina (B. Aires), 40: 428-432, 1980.
3. BRODSKYN, C.I.; SILVA, A.M.M. da; TAKEHARA, H.A. & MOTA, I. - Characterization of antibody isotype responsible for immune clearance in mice infected with T. cruzi. Immunol. Lett., 18: 255-258, 1988.
4. BRODSKYN, C.I.; SILVA, A.M.M. da; TAKEHARA, H.A. & MOTA I. - IgG subclasses responsible for immune clearance in mice infected with Trypanosoma cruzi. Immunol. Cell Biol., 67: 343-348, 1989.
6. GEA, S.; RODRIGUEZ, P. & VOTTERO-CIMA, E. - Characterization of Trypanosoma cruzi antigens recognized by sera from patients with chronic Chagas disease. Int. Arch. Allergy, 84: 410-413, 1987.
7. GEA, S.; GRUPPI, A.; BASSO, B.; MENSO, E. & VOTTERO-CIMA, E. - Antibodies to T. cruzi cytosol acidic antigens (F IV) in Chagas disease recognize parasite cell surface and human heart epitopes. J. clin. lab. Immunol. (in press).
8. GRUPPI, A.; MORETTI, E.R.A.; BASSO, B. & VOTTERO-CIMA, E. - Exoantigenos del Trypanosoma cruzi Epitopes reactivos con inmunoglobulinas de pacientes con enfermedad de Chagas. Medicina (B. Aires), 48: 161, 1988.
9. HEINZEL, F.P.; SADICK, M.D.; HOLADAY, B.J.; COFFMAN, R.L. & LOCKSLEY, R.M. - Reciprocal expression of interferon Y or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J. exp. Med., 169: 59-72, 1989.
10. HONTEBEYRIE-JOSKOWICZ, M.; SAID, G.; MILON, G.; MARCHAL, G. & EISEN, H. - L3T4 T cells able to mediate parasite-specific delayed-type hypersensitivity play a role in the pathology of experimental Chagas disease. Europ. J. Immunol., 17: 1027-1033, 1987.
11. IOSA, D.; DE QUATTRO, V.; DE PING LEE, D.; ELKAYAM, U. & PALMERO, H. - Plasma norepineph-rine in Chagas cardioneuromyopathy a marker of progressive dysautonomia. Amer. Heart J., 117: 882-887 1989.
12. KRETTLI, A.U. & BRENER, Z. - Resistance against T. cruzi associated to anti-living trypomastigotes antibodies. J. Immunol., 128: 2009-2012, 1982.
13. MOTA, I. & UMEKITA, L.F. - The effect C3 depletion on the clearance of T. cruzi induced by IgG antibodies. Immunol. Lett., 21: 221-225, 1989.
14. REED, S. - In vivo administration of recombinant INF-gamma induce macrophage activation, and prevents acute disease, immune supression and death in experimental T. cruzi infection. J. Immunol., 140: 4342-4347, 1988.
15. RIBEIRO dos SANTOS, R.; PIRMEZ, C. & SAVINO, W. - Rol of autoreactive immunological mechanisms in chagasic carditis. Res. Immunol., 142: 134-137, 1991
16. RIBEIRO dos SANTOS, R.; ROSSI, M.A.; LAUS, J.L.; SILVA, J.S.; SAVINO, W. & MENGEL, J.O. - And CD4 abrogates rejection and restablishes long term tolerance to singeneic newborn hearts grafted in mice chronically infected with Trypanosoma cruzi. J. exp. Med., (in press) 1991.
17. ROTEMBERG, M.E.; CARDONI, R.L.; DE TITTO, E.H.; MORENO, M. & SEGURA, E.L. - Trypanosoma cruzi: immune response in mice immunized with parasite antigens. Exp. Parasit., 65: 101-108, 1988.
18. TAKEHARA, H.A.; CARDOSO, D.F.; SILVA, A.M. da MOTA, J. - Lytic antibodies elicited by Trypanosoma cruzi infection recognize epitopes present on both bloodstream trypomastigote and epimastigote forms of parasite. Rev. Inst. Med. trop. S. Paulo, 30: 351-356, 1988.
19. TAMBOURGY, D.V.; KIPNIS, T.L. & DIAS DA SILVA, W. - Trypanosoma cruzi: antibody dependent killing of bloodstream trypomastigotes by mouse bone marrow-derivated mast cells and by mastocytoma cells. Exp. Parasit., 68: 192-201, 1989.
20. TRISCHMAN, T.; TANOWITZ, H.; WITTNER, M. & BLOOM, B. - Trypanosoma cruzi: role of immune response in the natural resistance of imbred strain of mice. Exp. Parasit., 45: 160-168, 1978.
21. UMEKITA, L.F.; TAKEHARA, H.A. & MOTA, I. - Role of the antibody Fc in the immune clearance of Trypanosoma cruzi. Immunol. Lett., 17: 85-89, 1988.
22. VIGNALI, D.A.A.; BICKLE, Q.D. & TAYLOR, M.C. - Immunity to Schistosoma mansoni in vivo. Contradiction or clarification? Immunol. Today, 10: 410-416, 1989.
23. VOLLER, A.; BIDWELL, D.N. & BARTLETT, A. - Dynatech Laboratories. Alexandria V. A., 1979.
24. VOTTERO-CIMA, E.; FAILLACI, G.; RUBIOLO, E.; GEA, S. & PISTORESI, M.C. - Heterogeneidad de la respuesta inmune humoral en humanos infectados con T. cruzi. Medicina (B. Aires),40: 121, 1980.

Address for correspondence:

Susana Gea

Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Ciudad Universitária

Sucursal 16

C.C. 61. 5016. Córdoba. Argentina

Publication Dates

Publication in this collection
13 Sept 2006
Date of issue
Oct 1992

History

Accepted
28 Apr 1992
Received
14 Jan 1991

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ARAUJO, F.G. - Development of resistance to Trypanosoma cruzi in mice depends on a viable population of L₃T₄(CD₄) T lymphocytes. Infect. Immun., 57: 2246-2248, 1989.

[2] 2. BASSO, B.; MORETTI, E.R.A. & DOMINGUEZ, M. - Cultivo de Trypanosoma cruzi en medio monofasico con aireacion para la obtención de antigenos. Medicina (B. Aires), 40: 428-432, 1980.

[3] 3. BRODSKYN, C.I.; SILVA, A.M.M. da; TAKEHARA, H.A. & MOTA, I. - Characterization of antibody isotype responsible for immune clearance in mice infected with T. cruzi. Immunol. Lett., 18: 255-258, 1988.

[4] 4. BRODSKYN, C.I.; SILVA, A.M.M. da; TAKEHARA, H.A. & MOTA I. - IgG subclasses responsible for immune clearance in mice infected with Trypanosoma cruzi. Immunol. Cell Biol., 67: 343-348, 1989.

[6] 6. GEA, S.; RODRIGUEZ, P. & VOTTERO-CIMA, E. - Characterization of Trypanosoma cruzi antigens recognized by sera from patients with chronic Chagas disease. Int. Arch. Allergy, 84: 410-413, 1987.

[7] 7. GEA, S.; GRUPPI, A.; BASSO, B.; MENSO, E. & VOTTERO-CIMA, E. - Antibodies to T. cruzi cytosol acidic antigens (F IV) in Chagas disease recognize parasite cell surface and human heart epitopes. J. clin. lab. Immunol. (in press).

[8] 8. GRUPPI, A.; MORETTI, E.R.A.; BASSO, B. & VOTTERO-CIMA, E. - Exoantigenos del Trypanosoma cruzi Epitopes reactivos con inmunoglobulinas de pacientes con enfermedad de Chagas. Medicina (B. Aires), 48: 161, 1988.

[9] 9. HEINZEL, F.P.; SADICK, M.D.; HOLADAY, B.J.; COFFMAN, R.L. & LOCKSLEY, R.M. - Reciprocal expression of interferon Y or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J. exp. Med., 169: 59-72, 1989.

[10] 10. HONTEBEYRIE-JOSKOWICZ, M.; SAID, G.; MILON, G.; MARCHAL, G. & EISEN, H. - L3T4 T cells able to mediate parasite-specific delayed-type hypersensitivity play a role in the pathology of experimental Chagas disease. Europ. J. Immunol., 17: 1027-1033, 1987.

[11] 11. IOSA, D.; DE QUATTRO, V.; DE PING LEE, D.; ELKAYAM, U. & PALMERO, H. - Plasma norepineph-rine in Chagas cardioneuromyopathy a marker of progressive dysautonomia. Amer. Heart J., 117: 882-887 1989.

[12] 12. KRETTLI, A.U. & BRENER, Z. - Resistance against T. cruzi associated to anti-living trypomastigotes antibodies. J. Immunol., 128: 2009-2012, 1982.

[13] 13. MOTA, I. & UMEKITA, L.F. - The effect C3 depletion on the clearance of T. cruzi induced by IgG antibodies. Immunol. Lett., 21: 221-225, 1989.

[14] 14. REED, S. - In vivo administration of recombinant INF-gamma induce macrophage activation, and prevents acute disease, immune supression and death in experimental T. cruzi infection. J. Immunol., 140: 4342-4347, 1988.

[15] 15. RIBEIRO dos SANTOS, R.; PIRMEZ, C. & SAVINO, W. - Rol of autoreactive immunological mechanisms in chagasic carditis. Res. Immunol., 142: 134-137, 1991

[16] 16. RIBEIRO dos SANTOS, R.; ROSSI, M.A.; LAUS, J.L.; SILVA, J.S.; SAVINO, W. & MENGEL, J.O. - And CD4 abrogates rejection and restablishes long term tolerance to singeneic newborn hearts grafted in mice chronically infected with Trypanosoma cruzi. J. exp. Med., (in press) 1991.

[17] 17. ROTEMBERG, M.E.; CARDONI, R.L.; DE TITTO, E.H.; MORENO, M. & SEGURA, E.L. - Trypanosoma cruzi: immune response in mice immunized with parasite antigens. Exp. Parasit., 65: 101-108, 1988.

[18] 18. TAKEHARA, H.A.; CARDOSO, D.F.; SILVA, A.M. da MOTA, J. - Lytic antibodies elicited by Trypanosoma cruzi infection recognize epitopes present on both bloodstream trypomastigote and epimastigote forms of parasite. Rev. Inst. Med. trop. S. Paulo, 30: 351-356, 1988.

[19] 19. TAMBOURGY, D.V.; KIPNIS, T.L. & DIAS DA SILVA, W. - Trypanosoma cruzi: antibody dependent killing of bloodstream trypomastigotes by mouse bone marrow-derivated mast cells and by mastocytoma cells. Exp. Parasit., 68: 192-201, 1989.

[20] 20. TRISCHMAN, T.; TANOWITZ, H.; WITTNER, M. & BLOOM, B. - Trypanosoma cruzi: role of immune response in the natural resistance of imbred strain of mice. Exp. Parasit., 45: 160-168, 1978.

[21] 21. UMEKITA, L.F.; TAKEHARA, H.A. & MOTA, I. - Role of the antibody Fc in the immune clearance of Trypanosoma cruzi. Immunol. Lett., 17: 85-89, 1988.

[22] 22. VIGNALI, D.A.A.; BICKLE, Q.D. & TAYLOR, M.C. - Immunity to Schistosoma mansoni in vivo. Contradiction or clarification? Immunol. Today, 10: 410-416, 1989.

[23] 23. VOLLER, A.; BIDWELL, D.N. & BARTLETT, A. - Dynatech Laboratories. Alexandria V. A., 1979.

[24] 24. VOTTERO-CIMA, E.; FAILLACI, G.; RUBIOLO, E.; GEA, S. & PISTORESI, M.C. - Heterogeneidad de la respuesta inmune humoral en humanos infectados con T. cruzi. Medicina (B. Aires),40: 121, 1980.

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