Trypanosoma cruzi: Role of the immune response in the natural resistance of inbred strains of mice

Trischmann, Thomas M.; Tanowitz, Herbert B.; Wittner, Murray; Bloom, Barry R.

doi:10.1016/0014-4894(78)90055-3

Cited by 145 publications

(65 citation statements)

References 18 publications

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“…This finding suggests that the IgG response in the acute phase is important for the control of the infection. A role played by humoral immunity was shown with congenitally athymic mice deficient in the T cell compartment, which are hypersusceptible to T. cruzi (426). Athymic mice treated with immune serum had low-level parasitemia and prolonged survival compared to athymic control mice that received normal serum and that showed high levels of parasitemia and mortality in a short period of time.…”

Section: Acquired Immunitymentioning

confidence: 99%

“…Additionally, the generation of parasite-specific CD8 ϩ T cell immunity is unaffected by the absence of type I interferon signaling (38,265). The importance of CD8 ϩ T cells in T. cruzi-infected mice has been challenged by experiments with a restriction of its immunodominance, which avoids pathogen elimination and inversely correlates with the severity of lesions (426)(427)(428). However, the cryptic infection induced CD4 ϩ T cells to senescence (11).…”

Section: Acquired Immunitymentioning

confidence: 99%

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Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

et al. 2011

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SUMMARY Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8 + γδ, and CD8α + T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease.

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Section: Acquired Immunitymentioning

confidence: 99%

Section: Acquired Immunitymentioning

confidence: 99%

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

et al. 2011

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“…5012 (Ralston Purina Co., St. Louis, MO) and given tap water ad lib. These mouse strains were chosen because of their resistance (B6) or susceptibility (C3H) to the Brazil strain of T. cruzi (9).…”

Section: Introductionmentioning

confidence: 99%

Role of iron in Trypanosoma cruzi infection of mice.

Lalonde¹,

Holbein²

1984

J. Clin. Invest.

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As bstract. The role of iron in experimental infection of mice with Trypanosoma cruzi was investigated. B6 mice had a transient parasitemia and a transient anemia, both of maximal intensity 28 d after the inoculation of T. cruzi. There was a biphasic hypoferremic host response to infection with T. cruzi with the peak hypoferremia also occurring 28 d after inoculation ofthe parasite. The mortality rate from infection was increased from 23% in phosphate-buffered saline-treated B6 mice to 50% in a group of B6 mice receiving iron-dextran (P < 0.025), whereas depletion of iron stores with the iron chelator desferrioxamine B and an iron-deficient diet provided complete protection of B6 mice (P < 0.05). The mortality rate in the highly susceptible C3H strain was reduced from 100% in the control group to 45% (P . 0.025) in the iron-depleted group. The tissue iron stores were altered in mice receiving either iron-dextran or desferrioxamine B and an iron-deficient diet. In vitro, T. cruzi was shown to require both a heme and a nonheme iron source for an optimal growth rate. The effects of iron excess or depletion on the outcome of infection with T. cruzi correlated both with the growth requirements of the parasite for iron and with the availability of intracellular iron. Thus, it was suggested that the hypoferremic response, by sequestering iron within intracellular stores, potentially enhanced the pathogenicity of the intracellular parasites. Furthermore, the in vivo effects of iron excess and depletion correlated with an effect of iron on the growth rate and pathogenicity of the parasite. Dr. Lalonde was also supported by a fellowship from the Medical Research Council of Canada during part of the study period.

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“…According to this view, the level of chronic commitment of a particular organ reflects to a certain extent its local parasite load. This parameter depends on parasite elements, such as virulence, inoculum size (11), tropism (1,12,26,28), immunogenicity, and systemic and local host factors, such as those controlling the magnitude and quality of the anti-T. cruzi immune response (24,25,30).…”

mentioning

confidence: 99%

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

Marinho¹,

Bucci²,

Dagli

et al. 2004

Infect Immun

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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 ؋ C3H/HePAS) and F 2 (A/J ؋ 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.

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Trypanosoma cruzi: Role of the immune response in the natural resistance of inbred strains of mice

Cited by 145 publications

References 18 publications

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

Role of iron in Trypanosoma cruzi infection of mice.

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

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