TY - JOUR
T1 - Trypanosoma cruzi calreticulin
T2 - A possible role in Chagas' disease autoimmunity
AU - Ribeiro, Carolina Hager
AU - López, Nandy C.
AU - Ramírez, Galia A.
AU - Valck, Carolina E.
AU - Molina, María Carmen
AU - Aguilar, Lorena
AU - Rodríguez, Margarita
AU - Maldonado, Ismael
AU - Martínez, Ramón
AU - González, Carlos
AU - Troncoso, Rodrigo
AU - Lavandero, Sergio
AU - Gingras, Alexandre R.
AU - Schwaeble, Wilhelm
AU - Ferreira, Arturo
N1 - Funding Information:
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.
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molimm.2008.10.034
DO - 10.1016/j.molimm.2008.10.034
M3 - Article
C2 - 19108895
AN - SCOPUS:60949092870
SN - 0161-5890
VL - 46
SP - 1092
EP - 1099
JO - Molecular Immunology
JF - Molecular Immunology
IS - 6
ER -