International Immunology Advance Access originally published online on January 14, 2008
International Immunology 2008 20(4):461-470; doi:10.1093/intimm/dxm149
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Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice
1 Departamento de Investigación, Instituto Nacional de Parasitología ‘Dr Mario Fatala Chaben’, ANLIS-Malbrán, Ministerio de Salud, Argentina Av. Paseo Colón 568, Buenos Aires 1063, Argentina
2 Departamento de Bioestadística, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina
3 Hospital Interzonal General de Agudos ‘Eva Perón’, San Martín, Provincia de Buenos Aires, Argentina
4 CIHIDECAR, Departamento de Química Orgánica, Pabellon II, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina
Correspondence to: V. G. Duschak; E-mail: vduschak{at}yahoo.es
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.
Keywords: C-T domain, cruzipain, glycoprotein, sulfated epitopes, Trypanosoma cruzi
* These authors contributed equally to this study.
Transmitting editor: K. Okumura
Received 25 May 2007, accepted 12 December 2007.