Pathology affects different organs in two mouse strains chronically infected by a Trypanosoma cruzi clone: a model for genetic studies of Chagas' disease.
Chagas' disease is a chronic infection caused by Trypanosoma cruzi and represents an important public health burden in Latin America. Frequently the disease evolves undetectable for decades, while in a significant fraction of the affected individuals it culminates in death by heart failure. Here, we describe a novel murine model of the chronic infection with T. cruzi using a stable clone isolated from a human patient (Sylvio X10/4). The infection in the C3H/HePAS mouse strain progresses chronically and is mainly characterized by intense cardiac inflammatory lesions that recapitulate the chronic cardiac pathology observed in the human disease. Moderate striated muscle lesions are also present in C3H/HePAS mice. Viable parasites are detected and recovered from the chronic heart lesions of C3H/HePAS mice, supporting the current notion that development of heart pathology in Chagas' disease is related to parasite persistence in the inflamed tissue. By contrast, in infected A/J mice, chronic inflammatory lesions are targeted to the liver and the skeletal muscle, while pathology and parasites are undetectable in the heart. The phenotypic analysis of F(1) (A/J x C3H/HePAS) and F(2) (A/J x C3H/HePAS) mice suggests that the genetic predisposition to develop the inflammatory lesions caused by T. cruzi (Sylvio X10/4 clone) is heterogeneous because the heart and liver pathology segregate in the F(2) generation. These findings raise the hypothesis that the pathology heterogeneity observed in humans with Chagas' disease (absence and presence of cardiac or digestive chronic lesions) may be attributable to host genetic factors.
Marinho
Claudio R F
CR
Department of Immunology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo, Brazil. marinho@usp.br
Bucci
Daniella Z
DZ
Dagli
Maria Lúcia Z
ML
Bastos
Karina R B
KR
Grisotto
Marcos G
MG
Sardinha
Luiz R
LR
Baptista
Cristiane R G M
CR
Gonçalves
Carlos Penha
CP
Lima
Maria Regina D'Império
MR
Alvarez
José M
JM
D000818:Animals; D002598:Chagas Cardiomyopathy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D014355:Chagas Disease / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002908:Chronic Disease; D020022:Genetic Predisposition to Disease; D006321:Heart / Q000469:parasitology*; D006801:Humans; D008099:Liver / Q000469:parasitology* / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000469:parasitology* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D014349:Trypanosoma cruzi / Q000472:pathogenicity*