Structural and immunological characterization of sulphatides: relevance of sulphate moieties in Trypanosoma cruzi glycoconjugates.
Sulphoglycosphingolipids, present on the surface of diverse cells, participate in the regulation of various cellular events. However, little is known about the structure and the role of sulphoglycosphingolipids in trypanosomatids. Herein, sulphated dihexosylceramide structures - composed mainly of sphingosine as the long chain base acylated with stearic acid - have been determined for the first time in Trypanosoma cruzi epimastigotes by UV-MALDI-TOF-MS analysis. Interestingly, inhibition ELISA assays using cruzipain as antigen and polyclonal rabbit antibodies specific for cruzipain, the major cysteine proteinase of T. cruzi, or for its C-terminal domain, have demonstrated (i) that sulphate epitopes are shared between cruzipain and sulphatides of T. cruzi, (ii) that cross-reactivity maps to the C-terminal domain and (iii) the existence of other antigenic determinants in the glycolipidic structures. These features provide evidence that sulphate groups are antigenic in sulphate-containing parasite glycoconjugates. Furthermore, IgG2 antibody levels inversely correlate with disease severity in chronic Chagas disease patients, suggesting that IgG2 antibodies specific for sulphated epitopes might be associated with protective immunity and might be considered as potential surrogates of the course of chronic Chagas disease.
Instituto Nacional de Parasitología Dr Mario Fatala Chaben, ANLIS-Malbrán, Ministerio de Salud de la Nación, Buenos Aires, Argentina.
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Acosta
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Soprano
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Ferrero
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Esteva
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Riarte
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Duschak
D000328:Adult; D000818:Animals; D000981:Antiprotozoal Agents / Q000097:blood; D014355:Chagas Disease / Q000276:immunology; D003429:Cross Reactions; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006001:Glycoconjugates / Q000032:analysis* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D015800:Protozoan Proteins; D011817:Rabbits; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013433:Sulfoglycosphingolipids / Q000032:analysis* / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000737:chemistry* / Q000276:immunology*
D000981:Antiprotozoal Agents; D006001:Glycoconjugates; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D013433:Sulfoglycosphingolipids; D003546:Cysteine Endopeptidases; C063214:cruzipain