Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice

Diana Maria Acosta, Maria Rosa Arnaiz, Mónica Inés Esteva, Mariana Barboza Gardner, Diana Stivale, Ulises Daniel Orlando, Susana Torres, Susana Adriana Laucella, Alicia Susana Couto, Vilma Gladys Duschak

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)461-470
Number of pages10
JournalInternational Immunology
Volume20
Issue number4
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

Fingerprint

Sulfates
Trypanosoma cruzi
Humoral Immunity
Immunoglobulin G
Cysteine Proteases
Chagas Disease
Congenital Heart Defects
Delayed Hypersensitivity
Infection
Oligosaccharides
Cellular Immunity
cruzipain
Epitopes
Immunization
Glycoproteins
T-Lymphocytes
Antigens
Antibodies
Serum

Keywords

  • C-T domain
  • Cruzipain
  • Glycoprotein
  • Sulfated epitopes
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Immunology

Cite this

Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice. / Acosta, Diana Maria; Arnaiz, Maria Rosa; Esteva, Mónica Inés; Barboza Gardner, Mariana; Stivale, Diana; Orlando, Ulises Daniel; Torres, Susana; Laucella, Susana Adriana; Couto, Alicia Susana; Duschak, Vilma Gladys.

In: International Immunology, Vol. 20, No. 4, 01.04.2008, p. 461-470.

Research output: Contribution to journalArticle

Acosta, DM, Arnaiz, MR, Esteva, MI, Barboza Gardner, M, Stivale, D, Orlando, UD, Torres, S, Laucella, SA, Couto, AS & Duschak, VG 2008, '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, pp. 461-470. https://doi.org/10.1093/intimm/dxm149
Acosta, Diana Maria ; Arnaiz, Maria Rosa ; Esteva, Mónica Inés ; Barboza Gardner, Mariana ; Stivale, Diana ; Orlando, Ulises Daniel ; Torres, Susana ; Laucella, Susana Adriana ; Couto, Alicia Susana ; Duschak, Vilma Gladys. / Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice. In: International Immunology. 2008 ; Vol. 20, No. 4. pp. 461-470.
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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.",
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AU - Arnaiz, Maria Rosa

AU - Esteva, Mónica Inés

AU - Barboza Gardner, Mariana

AU - Stivale, Diana

AU - Orlando, Ulises Daniel

AU - Torres, Susana

AU - Laucella, Susana Adriana

AU - Couto, Alicia Susana

AU - Duschak, Vilma Gladys

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N2 - 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.

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