3 results on '"C-T domain"'
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2. Cruzipain Sulfotopes-Specific Antibodies Generate Cardiac Tissue Abnormalities and Favor Trypanosoma cruzi Infection in the BALB/c Mice Model of Experimental Chagas Disease.
- Author
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Soprano, Luciana L., Ferrero, Maximiliano R., Landoni, Malena, García, Gabriela A., Esteva, Mónica I., Couto, Alicia S., and Duschak, Vilma G.
- Subjects
CHAGAS' disease ,TRYPANOSOMA cruzi ,ANIMAL disease models ,SERUM albumin ,LABORATORY mice ,TISSUES ,IMMUNOGLOBULINS - Abstract
Trypanosoma cruzi cruzipain (Cz) bears a C-terminal domain (C-T) that contains sulfated epitopes "sulfotopes" (GlcNAc6S) on its unique N-glycosylation site. The effects of in vivo exposure to GlcNAc6S on heart tissue ultrastructure, immune responses, and along the outcome of infection by T. cruzi , were evaluated in a murine experimental model, BALB/c, using three independent strategies. First, mice were pre-exposed to C-T by immunization. C-T-immunized mice (C-T
IM ) showed IgG2a/IgG1 <1, induced the production of cytokines from Th2, Th17, and Th1 profiles with respect to those of dC-TIM , which only induced IL-10 respect to the control mice. Surprisingly, after sublethal challenge, both C-TIM and dC-TIM showed significantly higher parasitemia and mortality than the control group. Second, mice exposed to BSA-GlcNAc6S as immunogen (BSA-GlcNAc6SIM ) showed: severe ultrastructural cardiac alterations while BSA-GlcNAcIM conserved the regular tissue architecture with slight myofibril changes; a strong highly specific humoral-immune-response reproducing the IgG-isotype-profile obtained with C-TIM ; and a significant memory-T-cell-response demonstrating sulfotope-immunodominance with respect to BSA-GlcNAcIM . After sublethal challenge, BSA-GlcNAc6SIM showed exacerbated parasitemias, despite elevated IFN-γ levels were registered. In both cases, the abrogation of ultrastructural alterations when using desulfated immunogens supported the direct involvement of sulfotopes and/or indirect effect through their specific antibodies, in the induction of tissue damage. Finally, a third strategy using a passive transference of sulfotope-specific antibodies (IgG-GlcNAc6S) showed the detrimental activity of IgG-GlcNAc6S on mice cardiac tissue, and mice treated with IgG-GlcNAc6S after a sublethal dose of T. cruzi , surprisingly reached higher parasitemias than control groups. These findings confirmed the indirect role of the sulfotopes, via their IgG-GlcNAc6S, both in the immunopathogenicity as well as favoring T. cruzi infection. [ABSTRACT FROM AUTHOR]- Published
- 2022
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3. Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice
- Author
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Acosta, D.M., Arnaiz, M.R., Esteva, M.I., Barboza, M., Stivale, D., Orlando, U.D., Torres, S., Laucella, S.A., Couto, A.S., and Duschak, V.G.
- Subjects
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 - 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. © 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.
- Published
- 2008
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