Chronic murine myocarditis due to Trypanosoma cruzi: an ultrastructural study and immunochemical characterization of cardiac interstitial matrix

Abstract

In an attempt to define the mouse-model for chronic Chagas' disease, a serological, histopathological and ultrastructural study as well as immunotyping of myocardium collagenic matrix were performed on Swiss mice, chronically infected with Trypanosoma cruzi strains: 21 SF and Mambaí (Type II); PMN and Bolivia (Type III), spontaneously surviving after 154 to 468 days of infection. Haemagglutination and indirect immunofluorescence tests showed high titres of specific antibodies. The ultrastructural study disclosed the cellular constitution of the inflammatory infiltrate showing the predominance of monocytes, macrophages with intense phagocytic activity, fibroblasts, myofibroblasts and abundant collagen matrix suggesting the association of the inflammatory process with fibrogenesis in chronic chagasic cardiomyopathy. Arteriolar and blood capillary alterations together with dissociation of cardiac cells from the capillary wall by edema and inflammation were related to ultrastructural lesions of myocardial cells. Rupture of parasitized cardiac myocells contribute to intensify the inflammatory process in focal areas. Collagen immunotyping showed the predominance of Types III and IV collagen. Collagen degradation and phagocytosis were present suggesting a reversibility of the fibrous process. The mouse model seems to be valuable in the study of the pathogenetic mechanisms in Chagas cardiomyopathy, providing that T. cruzi strains of low virulence and high pathogenicity are used.

Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

“…These physical characteristics are consistent with other murine models, featuring alterations in fur colour with piloerection, hunched posture and severe paralysis of the lower extremities (da Silva et al 2012). Kinetics of parasitaemia in this model also showed similar levels to other well-studied strains in chronic phase (Table I), such as T. cruzi Tulahuén, 21SF, Mambai, Bolivia, TBAR/MX/0000/Queretaro and MHOM/MX/1994/Ninoa (Andrade & Grimaud 1986, Petray et al 1995, Espinoza et al 2010). Therefore, we are led to conclude that our model is physically similar to other murine models of Chagas disease.…”

Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease

“…Although several studies were carried out using different animal models that reproduce aspects of the chronic disease (Laranja et al 1956, Federici et al 1964, Andrade & Grimaud 1986, Figueiredo et al 1986, Sadigursky & Andrade 1986, de Lana et al 1988, Rosner et al 1989, Ramírez et al 1994, Andrade et al 1997, Carvalho et al 2003, 2012, Silverio et al 2012), reasonable experimental models that simultaneously reproduce relevant parasitological and clinical aspects of the chronic Chagas’ heart disease in association with immunological abnormalities are still needed.…”

“…Furthermore, the therapeutic tools used to treat chronic patients only mitigate symptoms of Chagas’ heart disease; therefore, new therapeutic agents are needed (Lannes-Vieira et al 2010). In research aimed at elucidating the pathophysiology of CD or to screen potential therapeutic agents, chronic infection with T. cruzi reproduced myocarditis and fibrosis in experimentally-infected dogs (de Lana et al 1988), mice (Federici et al 1964, Andrade & Grimaud 1986), hamsters (Ramírez et al 1994) and monkeys (Carvalho et al 2003, 2012). Furthermore, some aspects of the electrical abnormalities associated with chronic CD were reproduced in rabbits (Figueiredo et al 1986), mice (Sadigursky & Andrade 1986, Silverio et al 2012), dogs (Andrade et al 1997) and monkeys (Rosner et al 1989, Carvalho et al 2003, 2012).…”

Fibrogenesis and collagen resorption in the heart and skeletal muscle of Calomys callosus experimentally infected with Trypanosoma cruzi: immunohistochemical identification of extracellular matrix components

“…Several authors have emphasized the influence of the genetic type of collagen in the resorption of the fibrosis in the liver (Rojkind & Dunn 1979, Grimaud et al 1980. However, Andrade and Grimaud (1986) and Andrade (1992), studying the regression of fibrosis in schistosomal granuloma have shown that both Types I and III collagens disappeared gradually and simultaneously.…”