title: Effect of Trypanosoma cruzi released antigens binding to non-infected cells on anti-parasite antibody recognition and expression of extracellular matrix components.
abstract: It has been proposed that antigens released by Trypanosoma cruzi sensitize vertebrate cells leading to their destruction by the immune response raised against the parasite. Here, we characterized antigens released by trypomastigotes of T. cruzi that bind to non-infected cells and investigated biological consequences of this adsorption. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of antigens released by [(35)S]-methionine-labeled parasites revealed the presence of polypeptides mainly ranging from 85 to 170 kDa that were specifically recognized by sera from chronically T. cruzi infected rabbits. Polypeptides of 85-110 and 160-170 kDa bound to non-infected epithelial, fibroblast and muscle mammalian cell lines, which thus became targets for anti-T. cruzi antibody binding. Cysteine-proteinase, but not trans-sialidase, was detected among the cell-bound antigens, and purified cysteine-proteinase was adsorbed to non-infected cells. Immunoelectron microscopic studies showed that parasite antigens were mainly released as membrane vesicles that adhered to membrane microvilli and were internalized by mammalian cells. We provide evidence that adsorption of parasite antigens induced an increase in expression of extracellular matrix (ECM) components (fibronectin, laminin and type I collagen) by sensitized cells. Thus, our data reinforce the idea that in vivo T. cruzi released antigens might be involved in the establishment of inflammation, sensitizing non-infected host cells and triggering an immune response against parasite antigens. Further, our data showed that antigen sensitization modulates biological cell functions as ECM expression that could mediate cell-cell or parasite-host cell interactions, contributing to the establishment of inflammation.
authors.affiliation: Departamento de Imunologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), Avenida Brasil, 4365, Manguinhos, Caixa Postal 926, CEP 21045-900, Rio de Janeiro, RJ, Brazil. rospinho@ioc.fiocruz.br
authors.forename: R T
authors.initials: RT
authors.lastname: Pinho
authors.forename: M A
authors.initials: MA
authors.lastname: Vannier-Santos
authors.forename: C R
authors.initials: CR
authors.lastname: Alves
authors.forename: A P M P
authors.initials: AP
authors.lastname: Marino
authors.forename: L R R
authors.initials: LR
authors.lastname: Castello Branco
authors.forename: J
authors.initials: J
authors.lastname: Lannes-Vieira
mesh_terms: D000327:Adsorption; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology* / Q000378:metabolism*; D000954:Antigens, Surface / Q000276:immunology*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000276:immunology*; D014643:Variant Surface Glycoproteins, Trypanosoma
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D014643:Variant Surface Glycoproteins, Trypanosoma; C070842:trypomastigote specific surface antigen