Variability of Kinetoplast DNA Gene Signatures of Trypanosoma cruzi II Strains from Patients with Different Clinical Forms of Chagas' Disease in Brazil

Trypanosoma cruzi, the etiological agent of Chagas disease, presents a high degree of intraspecific genetic variability, with possible implications for the clinical forms of the disease, like the development of cardiopathy, megaesophagus, and megacolon, alone or in combination. This tissue tropism involved in the pathogenesis of Chagas disease has still not been totally elucidated. Thus, the current review approaches key aspects of T. cruzi genetic diversity, the clinical forms of Chagas disease, and the infection of the host cell by the parasite and the immune response. Other aspects discussed here include the release of immunosuppressive factors by the parasite, acting in the host's immune response pathways; host cell apoptosis inhibition; the pathogenesis of chagasic megaesophagus, which can be related to host-parasite interaction; and finally the association between megaesophagus and increased risk for the development of squamous-cell esophageal carcinoma. However, despite great advances in the understanding of this disease, it is still not possible to establish the true relationship between the parasite's genetic variability and the clinical form of Chagas disease.

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Antibodies Reactive to Trypanosoma cruzi Epimastigotes or Amastigotes Express Different Idiotypic Patterns if from Patients with Different Clinical Forms of Chagas' Disease

Scandinavian Journal of Immunology ◽

10.1046/j.1365-3083.1996.d01-262.x ◽

1996 ◽

Vol 43 (6) ◽

pp. 671-679

Author(s):

R. RIBEIRO‐RODRIGUES ◽

D. G. COLLEY ◽

R. CORREA‐OLIVEIRA ◽

C. E. CARTER

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Clinical Forms

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Trypanosoma cruzi-Induced Activation of Functionally Distinct αβ and γδ CD4− CD8− T Cells in Individuals with Polar Forms of Chagas' Disease

Infection and Immunity ◽

10.1128/iai.00179-10 ◽

2010 ◽

Vol 78 (10) ◽

pp. 4421-4430 ◽

Cited By ~ 20

Author(s):

Fernanda Nobre Amaral Villani ◽

Manoel Otávio da Costa Rocha ◽

Maria do Carmo Pereira Nunes ◽

Lis Ribeiro do Valle Antonelli ◽

Luisa Mourão Dias Magalhães ◽

...

Keyword(s):

T Cells ◽

Trypanosoma Cruzi ◽

Chagas Disease ◽

Inflammatory Cytokines ◽

Interleukin 10 ◽

Protective Role ◽

Clinical Forms ◽

Polar Forms ◽

Clinical Measures

ABSTRACT CD4− CD8− (double-negative [DN]) T cells have recently been shown to display important immunological functions in human diseases. They express γδ or αβ T-cell receptors that recognize lipid/glycolipid antigens presented via the nonclassical major histocompatibility complex molecules of the CD1 family. We recently demonstrated that while αβ DN T cells serve primarily to express inflammatory cytokines, γδ DN T cells express mainly interleukin-10 (IL-10) in patients with cutaneous leishmaniasis. We also demonstrated a correlation between DN T cells and the expression of gamma interferon in the acute phase of Trypanosoma cruzi experimental infection. In this work, we sought to investigate whether αβ or γδ DN T cells display distinct immunoregulatory potentials in patients with polar forms of human Chagas' disease. Our data showed that in vitro infection with T. cruzi leads to expansion of DN T cells in patients with the indeterminate and severe cardiac clinical forms of the disease. However, while αβ DN T cells primarily produce inflammatory cytokines in both forms of the disease, γδ DN T cells display a marked, significant increase in antigen-specific IL-10 expression in indeterminate patients relative to cardiac patients. Finally, higher frequencies of the IL-10-producing γδ DN T cells were correlated with improved clinical measures of cardiac function in the patients, suggesting a protective role for these cells in Chagas' disease. Taken together, these data show distinct functional characteristics for αβ and γδ DN T cells associated with distinct morbidity rates and clinical forms in human Chagas' disease.

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The Trypanosoma cruzi kinetoplast DNA minicircle sequences transfer biomarker of the multidrug treatment of Chagas disease

10.1101/2021.12.16.473091 ◽

2021 ◽

Author(s):

Antonio R. L. Teixeira ◽

Alessandro O Sousa ◽

Clever C Gomes ◽

Adriana A Sá ◽

Rubens J Nascimento ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Nuclear Dna ◽

Germ Line ◽

Pcr Amplification ◽

Dna Transfer ◽

Heart Cells ◽

Kinetoplast Dna ◽

Chagas Cardiomyopathy ◽

Primer Sets

Background: The Trypanosoma cruzi infection renders the transfer of the mitochondrion kinetoplast DNA minicircle sequences into the host’s genome. The Aves are refractory to the infection, but chicks hatched from the T. cruzi inoculated eggs integrate the DNA minicircle sequences into the germ line cells. Rabbits, mice and chickens with the minicircle sequences mutations develop the Chagas cardiomyopathy and the DNA transfer underpins the heart disease. Methodology: The PCR with the specific primer sets revealed the Protist nuclear DNA and the kinetoplast DNA in the agarose gels bands probed with the radiolabel specific sequences from tissues of the T. cruzi-infected rabbits and of the mice. A targetprimer TAIL-PCR amplification employing primer sets from the chickens, rabbits and mice, in combination with primer sets from the the T. cruzi kinetoplast minicircle sequences was used. This approach led us to disclose the integration sites of the kinetoplast DNA biomarker, then, used to monitor the effect of multidrug treatment of the T. cruzi infected mice. Principal findings: The Southern hybridization, clone and sequence of the amplification products revealed the DNA minicircle sequences integrations sites in the LINE transposable elements. An array of inhibitors of eukaryote cells division was used to arrest the DNA transfer. It was shown that nine out of 12 inhibitors prevented the kinetoplast DNA integration into the macrophage genome. The multidrug treatment of the acutely T. cruzi-infected mice with Benznidazole, Azidothymidine and Ofloxacin lessened circa 2.5-fold the rate of the minicircle sequences integrations in the mouse genome and inhibited the rejection of the target heart cells. Conclusion and significance: The T. cruzi mitochondrion kinetoplast minicircle sequences transfer driven pathogenesis of Chagas disease is an ancient Cross-Kingdom DNA phenomenon of evolution and, therefore, paradigm research with effective purposing inhibitors is needed.

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