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

Carolina Hager Ribeiro, Nandy C. López, Galia A. Ramírez, Carolina E. Valck, María Carmen Molina, Lorena Aguilar, Margarita Rodríguez, Ismael Maldonado, Ramón Martínez, Carlos González, Rodrigo Troncoso, Sergio Lavandero, Alexandre R. Gingras, Wilhelm Schwaeble, Arturo Ferreira

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32 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)1092-1099
Número de páginas8
PublicaciónMolecular Immunology
Volumen46
N.º6
DOI
EstadoPublished - mar. 2009

Financiación

This research was sponsored by the following Chilean Public Research Grants: Bicentennial ACT 29 and R-07, both from CONICYT; FONDAP 1501006 and MECESUP-Red UCH 0115. We are grateful to Ruth Mora, Juana Orellana, Nancy Fabres, Miguel Sepúlveda, and Fidel Albornoz for their excellent expert technical assistance.

FinanciadoresNúmero del financiador
Comisión Nacional de Investigación Científica y TecnológicaMECESUP-Red UCH 0115

    ASJC Scopus Subject Areas

    • Immunology
    • Molecular Biology

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