Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice.
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.
Acosta
Diana Maria
DM
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.
Arnaiz
Maria Rosa
MR
Esteva
Mónica Inés
MI
Barboza
Mariana
M
Stivale
Diana
D
Orlando
Ulises Daniel
UD
Torres
Susana
S
Laucella
Susana Adriana
SA
Couto
Alicia Susana
AS
Duschak
Vilma Gladys
VG
D000818:Animals; D014355:Chagas Disease / Q000097:blood / Q000276:immunology*; D002908:Chronic Disease; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D004195:Disease Models, Animal; D005260:Female; D006331:Heart Diseases / Q000276:immunology* / Q000473:pathology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood*; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D010446:Peptide Fragments / Q000276:immunology; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins; D015203:Reproducibility of Results; D012698:Serologic Tests; D013431:Sulfates / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000201:enzymology / Q000276:immunology*
D007074:Immunoglobulin G; D010446:Peptide Fragments; D015800:Protozoan Proteins; D013431:Sulfates; D003546:Cysteine Endopeptidases; C063214:cruzipain