Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice
| Autor: | Acosta, D.M., Arnaiz, M.R., Esteva, M.I., Barboza, M., Stivale, D., Orlando, U.D., Torres, S., Laucella, S.A., Couto, A.S., Duschak, V.G. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
serology
sulfate delayed hypersensitivity Mice Bagg albino mouse humoral immunity heart injury Hypersensitivity Delayed epitope Mice Inbred BALB C Sulfates disease course article protein domain enzyme activity Cysteine Endopeptidases female priority journal parasitosis disease severity immunoreactivity Sulfated epitopes Heart Diseases Trypanosoma cruzi Injections Subcutaneous animal experiment memory T lymphocyte cellular immunity immunization animal tissue antigen cruzipain protein targeting Animals Humans immunoglobulin G2b controlled study Chagas Disease Serologic Tests immunoglobulin G antibody mouse carboxy terminal sequence nonhuman animal model Myocardium immunopathogenesis Reproducibility of Results Peptide Fragments Protein Structure Tertiary Disease Models Animal Immunoglobulin G Chronic Disease C-T domain Glycoprotein |
| Zdroj: | Int. Immunol. 2008;20(4):461-470 Biblioteca Digital (UBA-FCEN) Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales instacron:UBA-FCEN |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|