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 language | English (US) |
|---|---|
| Pages (from-to) | 461-470 |
| Number of pages | 10 |
| Journal | International Immunology |
| Volume | 20 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2008 |
| Externally published | Yes |
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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 journal › Article
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TY - JOUR
T1 - Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice
AU - Acosta, Diana Maria
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
PY - 2008/4/1
Y1 - 2008/4/1
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.
AB - 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.
KW - C-T domain
KW - Cruzipain
KW - Glycoprotein
KW - Sulfated epitopes
KW - Trypanosoma cruzi
UR - http://www.scopus.com/inward/record.url?scp=41149162762&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41149162762&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxm149
DO - 10.1093/intimm/dxm149
M3 - Article
C2 - 18195050
AN - SCOPUS:41149162762
VL - 20
SP - 461
EP - 470
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 4
ER -