Pathology Affects Different Organs in Two Mouse Strains Chronically Infected by a
            <i>Trypanosoma cruzi</i>
            Clone: a Model for Genetic Studies of Chagas’ Disease

Marinho, Cláudio R. F.; Bucci, Daniella Zanetti; Dagli, M.L.; Bastos, Karina R. B.; Grisotto, Marcos Augusto Grigolin; Sardinha, Luiz Roberto; Baptista, Cristiane R. G. M.; Gonçalves, Carlos Penha; Lima, Maria Regina D’Império; Álvarez, José María

doi:10.1128/iai.72.4.2350-2357.2004

Cited by 54 publications

(58 citation statements)

References 29 publications

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“…Although the frequency of cardiac involvement in the guinea pigs in this study (62.5%) was higher than that in infected humans who develop clinical pathology (20% to 30%), the spectral nature of the disease in guinea pigs may allow for analysis of predictors of disease progression. Parasites do not consistently persist in cardiac tissue in many mouse models, 54,55 making the heart tropism observed in guinea pigs relatively unusual and informative. Furthermore, heart failure in the guinea pig model parallels the human pathogenesis in terms of changes in calcium cycling, myosin isoforms, and myocardial function.…”

Section: Discussionmentioning

confidence: 99%

Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Castro-Sesquen

Gilman

Yauri

et al. 2011

The American Journal of Pathology

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The guinea pig (Cavia porcellus) is a natural reservoir for Trypanosoma cruzi but has seldom been used as an experimental infection model. We developed a guinea pig infection model for acute and chronic Chagas disease. Seventy-two guinea pigs were inoculated intradermally with 10 4 trypomastigotes of T. cruzi strain Y (experimental group); 18 guinea pigs were used as control group. Eight animals from the experimental group and two from the control group were Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is one of the most important parasitic infections of the Americas. Despite successful vector control programs in many countries, the disease remains a major public health problem in Latin America, with 8 to 10 million people currently infected, an annual incidence of 65,000 new cases in 15 countries, and 14,000 deaths associated with the infection per year. 1 Transmission to the mammalian host occurs when a T. cruzi-infected triatomine vector deposits infectious trypomastigotes in feces during a blood meal and the parasites invade through the bite wound or intact mucosal membranes. 2 Trypomastigotes can infect virtually any nucleated cell, where they transform to amastigotes and replicate in the host cell cytoplasm. Amastigotes convert back to trypomastigotes inside the cell and then rupture the cell and circulate in the bloodstream. After weeks, the host immune response usually controls the acute infection but does not completely clear the parasite. This results in lifelong chronic infection of the host.The initial weeks after T. cruzi infection are characterized by a high-level parasitemia and symptoms that vary from mild nonspecific febrile illness to life-threatening myocarditis and/or meningoencephalitis. 2 Acute symptoms and detectable parasitemia resolve spontaneously within 2 to 3 months, and the infected individual passes into the chronic phase of the disease. Nearly all individuals in the early period of chronic infection are asymptomatic and are said to have the indeterminate form of the disease. In most individuals, the infection remains silent for life and is detectable only by anti-T. cruzi serologic tests and, in a proportion of individuals, by molecular Supported by NIH training grant in infectious and tropical diseases 5 T35 AI065385 and NIH grant 1R01AI087776-01.

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Section: Discussionmentioning

confidence: 99%

Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Castro-Sesquen

Gilman

Yauri

et al. 2011

The American Journal of Pathology

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“…2 We infected mice with the Brazil strain, which is generally regarded as a cardiomyotropic strain. Histopathological examination of the liver revealed an intense vasculitis not previously appreciated although noted by us and others in cardiovascular system.…”

Section: Discussionmentioning

confidence: 99%

“…1 T. cruzi also infects the recticuloendothelial system including the liver, spleen and bone marrow. 1,2 Acute Chagas' disease and congenital Chagas' disease are associated with elevated liver enzymes which usually resolve as the parasitemia wanes. 1 Interestingly, hepatocytes in vivo are not commonly observed to be infected, while cultured hepatocytes in vitro are readily infected with trypomastigotes.…”

Section: Introductionmentioning

confidence: 99%

Cell Cycle Regulatory Proteins in the Liver in Murine Trypanosoma cruzi Infection

Bouzahzah

Nagajyothi²,

Desruisseaux³

et al. 2006

Cell Cycle

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The liver is an important target of Trypanosoma cruzi infection. Infection of CD-1 mice with T. cruzi (Brazil strain) resulted in parasitism of the liver, primarily in sinusoidal and Kupffer cells. Immunoblot analysis revealed activation of extra cellular signal-regulated kinase (ERK) during the acute and subacute period of infection, but p38 mitogen activated kinase (MAPK) and JNK were not activated. The activity of important cell cycle regulatory genes was also examined in the liver following infection. There was increased expression of cyclin D1, cyclin E and cyclin A as well as proliferating cell nuclear antigen (PCNA) at 45, 60 and 215 days post infection. In addition, the levels of the cyclin-dependent kinase inhibitors p27 KIP1 , p21 WAF1 and the tumor suppressor p53 were increased in the livers obtained from infected mice. Quantitative PCR revealed increased abundance of mRNA for cyclins A, D1 and E. Interestingly, cyclin A and E are ordinarily not found in the adult liver. Thus infection caused a reversion to a fetal/neonatal phenotype. These data provide a molecular basis for cell proliferation in the liver following T. cruzi infection.

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“…Estos resultados concuerdan con lo anteriormente descrito por Marinho y colaboradores (22) quienes, usando una cepa de T. cruzi I (clon Sylvio X10/4), encontraron que estos animales desarrollaron la fase crónica de la infección con lesiones comparables a las encontradas en la cardiopatía chagásica humana.…”

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“…La invasión a este tejido se estableció de manera temprana, observándose la presencia de miocarditis y miositis aguda grave linfomonocitaria, similar a lo encontrado en estudios previos con otras cepas de T. cruzi y de ratón (21)(22)(23). Además, se encontró presencia de focos inflamatorios en otros órganos como bazo, hígado, pulmón, intestino delgado y músculo esquelético; además, en este último se observaron amastigotes, resultados que concuerdan con los hallazgos de Cummins y Tarleton (24).…”

Section: Dunclassified

Evaluación de las pruebas de PCR TcH2AF-R y S35-S36 para la detección de Trypanosoma cruzi en tejido cardiaco de ratón

Barrera¹,

Guevara²,

Pavía³

et al. 2008

biomedica

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Introducción. El trasplante es una opción terapéutica en la cardiomiopatía chagásica. Para la detección temprana de una posible reactivación de la infección, se propone el uso de pruebas de reacción en cadena de la polimerasa (PCR) a partir de biopsias endomiocárdicas; el modelo de ratón es una aproximación preliminar para evaluar la aplicación de éstas. Objetivo. Evaluar la aplicación de las pruebas de PCR basadas en los iniciadores TcH2AF-R y S35-S36 para la detección de T. cruzi en tejido cardiaco de ratones infectados con el parásito. Materiales y métodos. Se infectaron por vía intraperitoneal dos grupos de ratones ICR de 15 y 10 individuos con 0,3 ml de PBS que contenían 1x10 6 tripomastigotes de la cepa MHOM/CO/ 2001/D.A. (T. cruzi I) o 1x10 4 tripomastigotes de la cepa MHOM/BR/00/Y (T. cruzi II), respectivamente. El seguimiento de la parasitemia se realizó mediante microhematocrito y presencia de parásitos en el corazón a los 30, 60 (modelo agudo), 100 y 150 (modelo crónico) días por medio de histopatología y de las PCR TcH2AF-R y S35-S36. Resultados. La histopatología mostró alteraciones en el miocardio y presencia de amastigotes en los modelos agudo y crónico. En contraste al microhematocrito y al análisis histopatológico, la PCR S35-S36 permitió la detección de ambas cepas del parásito. La PCR TcH2AF-R detectó la cepa T. cruzi I con un desempeño superior al microhematocrito y al análisis histopatológico. Conclusiones. El uso de ambas pruebas de PCR puede ser útil en la confirmación de la reactivación de la infección postrasplante.Palabras clave: Trypanosoma cruzi, enfermedad de Chagas, cardiomiopatía chagásica, reacción en cadena de la polimerasa. Evaluation of TcH2AF-R and S35-S36 primers in PCR tests for the detection of Trypanosoma cruzi in mouse cardiac tissueIntroduction. Heart transplant is a therapeutic option in the treatment of chagasic cardiomyopathy. For early detection of Chagas reactivation cases, the use of PCR tests using endomyocardial biopsies has been proposed. Development of an animal model will be the first step in evaluating the applicability of this approach. Objective. PCR tests based on the TcH2AF-R and S35-S36 primers were evaluated for the detection of T. cruzi in heart tissue of mice experimentally infected with the parasite. Parasitemia and cardiac parasitic infection were determined at 30, 60 (acute model), 100 and 150 (chronic model) days by means of histopathological examination and by PCR, using the TcH2AF-R and S35-S36 primers. Results. The histopathological findings revealed alterations in the heart and the presence of intracellular amastigotes in acute and chronic models. In contrast to parasitemia levels and

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Pathology Affects Different Organs in Two Mouse Strains Chronically Infected by a Trypanosoma cruzi Clone: a Model for Genetic Studies of Chagas’ Disease

Cited by 54 publications

References 29 publications

Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Cell Cycle Regulatory Proteins in the Liver in Murine Trypanosoma cruzi Infection

Evaluación de las pruebas de PCR TcH2AF-R y S35-S36 para la detección de Trypanosoma cruzi en tejido cardiaco de ratón

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