Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice
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 re...
Guardado en:
Autores principales: | , |
---|---|
Publicado: |
2008
|
Materias: | |
Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09538178_v20_n4_p461_Acosta http://hdl.handle.net/20.500.12110/paper_09538178_v20_n4_p461_Acosta |
Aporte de: |
id |
paper:paper_09538178_v20_n4_p461_Acosta |
---|---|
record_format |
dspace |
spelling |
paper:paper_09538178_v20_n4_p461_Acosta2023-06-08T15:55:32Z Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice Laucella, Susana Adriana Couto, Alicia Susana 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 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. Fil:Laucella, S.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Couto, A.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2008 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09538178_v20_n4_p461_Acosta http://hdl.handle.net/20.500.12110/paper_09538178_v20_n4_p461_Acosta |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
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 |
spellingShingle |
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 Laucella, Susana Adriana Couto, Alicia Susana Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice |
topic_facet |
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 |
description |
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. |
author |
Laucella, Susana Adriana Couto, Alicia Susana |
author_facet |
Laucella, Susana Adriana Couto, Alicia Susana |
author_sort |
Laucella, Susana Adriana |
title |
Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice |
title_short |
Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice |
title_full |
Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice |
title_fullStr |
Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice |
title_full_unstemmed |
Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice |
title_sort |
sulfates are main targets of immune responses to cruzipain and are involved in heart damage in balb/c immunized mice |
publishDate |
2008 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09538178_v20_n4_p461_Acosta http://hdl.handle.net/20.500.12110/paper_09538178_v20_n4_p461_Acosta |
work_keys_str_mv |
AT laucellasusanaadriana sulfatesaremaintargetsofimmuneresponsestocruzipainandareinvolvedinheartdamageinbalbcimmunizedmice AT coutoaliciasusana sulfatesaremaintargetsofimmuneresponsestocruzipainandareinvolvedinheartdamageinbalbcimmunizedmice |
_version_ |
1768543905861599232 |