Trypanosoma cruzi calreticulin: A possible role in Chagas' disease autoimmunity

Ribeiro, CH; Lopez, NC; Ramirez, GA; Valck, CE; Molina, MC; Aguilar, L; Rodríguez, M.; Maldonado I.; Martínez R.; González C; Troncoso R.; Lavandero S.; Gingras, AR; Schwaeble, W; Ferreira A.

Abstract

Trypanosoma cruzi (T. cruzi) is the causative agent of Chagas' disease, an endemic and chronic illness that affects 18 million people in Latin America. The mechanisms underlying its pathogenesis are controversial. There is a growing body of evidence supporting the view that T. cruzi infection elicits severe autoimmune responses in the host, which significantly contribute to the pathogenesis of Chagas' disease, and several recent studies have reported the presence of autoantibodies and effector T lymphocytes against parasite and self antigens in infected patients and experimentally infected animals. T. cruzi calreticulin (TcCRT) is a 45 kDa protein, immunogenic in humans, rabbits and mice. It has a high degree of homology with human (HuCRT) and mouse calreticulin (MoCRT), which would explain why an immune response to TcCRT could contribute to autoimmune reactions in Chagas' disease. Anti-TcCRT antibodies generated in A/J mice immunized with recombinant TcCRT (rTcCRT) reacted with rHuCRT and bound to neonatal and adult isogenic cardiomyocytes cultured in vitro. Interestingly, histological alterations, such as edema formation and cell infiltrates, which include CD3+ cells, were detected in heart sections from immunized animals. Therefore, in rTcCRT-immunized mice, an autoimmune reaction against host CRT, paralleled by histological cardiac alterations, suggests a role of the parasite molecule in the induction of immunologically mediated heart tissue damage. The data presented here propose that TcCRT participates in the induction of cardiac autoimmunity in Chagas' disease. © 2008 Elsevier Ltd. All rights reserved.

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Título según WOS: Trypanosoma cruzi calreticulin: A possible role in Chagas' disease autoimmunity
Título según SCOPUS: Trypanosoma cruzi calreticulin: A possible role in Chagas' disease autoimmunity
Título de la Revista: MOLECULAR IMMUNOLOGY
Volumen: 46
Número: 6
Editorial: PERGAMON-ELSEVIER SCIENCE LTD
Fecha de publicación: 2009
Página de inicio: 1092
Página final: 1099
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S0161589008007335
DOI:

10.1016/j.molimm.2008.10.034

Notas: ISI, SCOPUS