title: Development of chronic cardiomyopathy in canine Chagas disease correlates with high IFN-gamma, TNF-alpha, and low IL-10 production during the acute infection phase.
abstract: When infected with Trypanosoma cruzi, Beagle dogs develop symptoms similar to those of Chagas disease in human beings, and could be an important experimental model for a better understanding of the immunopathogenic mechanisms involved in chronic chagasic infection. This study evaluates IL-10, IFN-gamma and TNF-alpha production in the sera, culture supernatant, heart and cervical lymph nodes and their correlation with cardiomegaly, cardiac inflammation and fibrosis in Beagle dogs infected with T. cruzi. Pathological analysis showed severe splenomegaly, lymphadenopathy and myocarditis in all infected dogs during the acute phase of the disease, with cardiomegaly, inflammation and fibrosis observed in 83% of the animals infected by T. cruzi during the chronic phase. The data indicate that infected animals producing IL-10 in the heart during the chronic phase and showing high IL-10 production in the culture supernatant and serum during the acute phase had lower cardiac alterations (myocarditis, fibrosis and cardiomegaly) than those with high IFN-gamma and TNF-alpha levels. These animals produced low IL-10 levels in the culture supernatant and serum during the acute phase and did not produce IL-10 in the heart during the chronic phase of the disease. Our findings showed that Beagle dogs are a good model for studying the immunopathogenic mechanism of Chagas disease, since they reproduce the clinical and immunological findings described in chagasic patients. The data suggest that the development of the chronic cardiac form of the disease is related to a strong Th1 response during the acute phase of the disease, while the development of the indeterminate form results from a blend of Th1 and Th2 responses soon after infection, suggesting that the acute phase immune response is important for the genesis of chronic cardiac lesions.
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo State, Brazil. pauloguedes@usp.br
authors.forename: Paulo M M
authors.initials: PM
authors.lastname: Guedes
authors.forename: Vanja M
authors.initials: VM
authors.lastname: Veloso
authors.forename: Luis C C
authors.initials: LC
authors.lastname: Afonso
authors.forename: Marcelo V
authors.initials: MV
authors.lastname: Caliari
authors.forename: Cláudia M
authors.initials: CM
authors.lastname: Carneiro
authors.forename: Lívia F
authors.initials: LF
authors.lastname: Diniz
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Marques-da-Silva
authors.forename: Ivo S
authors.initials: IS
authors.lastname: Caldas
authors.forename: Maria A
authors.initials: MA
authors.lastname: Do Valle Matta
authors.forename: Sheler M
authors.initials: SM
authors.lastname: Souza
authors.forename: Marta
authors.initials: M
authors.lastname: Lana
authors.forename: Egler
authors.initials: E
authors.lastname: Chiari
authors.forename: Lúcia M C
authors.initials: LM
authors.lastname: Galvão
authors.forename: Maria T
authors.initials: MT
authors.lastname: Bahia
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000276:immunology / Q000469:parasitology; D002598:Chagas Cardiomyopathy / Q000276:immunology / Q000469:parasitology / Q000473:pathology / Q000662:veterinary*; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000276:immunology / Q000469:parasitology* / Q000473:pathology; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005355:Fibrosis / Q000276:immunology / Q000469:parasitology; D006651:Histocytochemistry / Q000662:veterinary; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013163:Splenomegaly / Q000276:immunology / Q000469:parasitology; D014349:Trypanosoma cruzi / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma