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The TcI and TcII Trypanosoma cruzi experimental infections induce distinct immune responses and cardiac fibrosis in dogs.

Duz AL, Vieira PM, Roatt BM, Aguiar-Soares RD, Cardoso JM, Oliveira FC, Reis LE, Tafuri WL, Veloso VM, Reis AB, Carneiro CM - Mem. Inst. Oswaldo Cruz (2014)

Bottom Line: In addition, CD8+ T-lymphocytes isolated from the peripheral blood produced higher levels of interleukin (IL)-4.In the chronic phase, a significant increase in the number of inflammatory cells was detected in the right atrium.In the chronic phase, significant heart inflammation and fibrosis were observed, demonstrating that strains of different DTUs interact differently with the host.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunopatologia, Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil.

ABSTRACT
Trypanosoma cruzi infection may be caused by different strains with distinct discrete typing units (DTUs) that can result in variable clinical forms of chronic Chagas disease. The present study evaluates the immune response and cardiac lesions in dogs experimentally infected with different T. cruzi strains with distinct DTUs, namely, the Colombian (Col) and Y strains of TcI and TcII DTU, respectively. During infection with the Col strain, increased levels of alanine aminotransferase, erythrocytes, haematocrit and haemoglobin were observed. In addition, CD8+ T-lymphocytes isolated from the peripheral blood produced higher levels of interleukin (IL)-4. The latter suggests that during the acute phase, infection with the Col strain may remain unnoticed by circulating mononuclear cells. In the chronic phase, a significant increase in the number of inflammatory cells was detected in the right atrium. Conversely, infection with the Y strain led to leucopoenia, thrombopoenia, inversion of the ratio of CD4+/CD8+ T-lymphocytes and alterations in monocyte number. The Y strain stimulated the production of interferon-γ by CD4+ and CD8+ T-lymphocytes and IL-4 by CD8+ T-cells. In the chronic phase, significant heart inflammation and fibrosis were observed, demonstrating that strains of different DTUs interact differently with the host.

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: immunophenotypic profile and cytokine patterns [interferon (INF)-γ andinterleukin (IL)-4] of CD4+ and CD8+ T-lymphocyte present in peripheral bloodbefore infection (0), nine, 60, 90 and 240 days after infection with Y strain(Y) or Colombian strain (Col) of Trypanosoma cruzi. T-cellssubsets were identified by flow cytometric immunostaining as described inMaterials and Methods. Data were expressed as the index, i.e., the meanpercentage of positive cells of cultures stimulated/mean percentage of positivecells of unstimulated cultures, within gated lymphocytes. A-D: index ofcytokine production by CD4+ or CD8+ in culture stimulated with epimastigoteantigens of the Y strain; E-H: index of cytokine production by CD4+ or CD8+ inculture stimulated with epimastigote antigens of the Col strain. The resultsare expressed as index ± standard error. Significant differences at p < 0.05are indicated by letters a, b and c for comparisons with days 9, 60 and 90,respectively. #: differences between the non-infected group (NI) and infectedgroups (Y or Col).
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f03: : immunophenotypic profile and cytokine patterns [interferon (INF)-γ andinterleukin (IL)-4] of CD4+ and CD8+ T-lymphocyte present in peripheral bloodbefore infection (0), nine, 60, 90 and 240 days after infection with Y strain(Y) or Colombian strain (Col) of Trypanosoma cruzi. T-cellssubsets were identified by flow cytometric immunostaining as described inMaterials and Methods. Data were expressed as the index, i.e., the meanpercentage of positive cells of cultures stimulated/mean percentage of positivecells of unstimulated cultures, within gated lymphocytes. A-D: index ofcytokine production by CD4+ or CD8+ in culture stimulated with epimastigoteantigens of the Y strain; E-H: index of cytokine production by CD4+ or CD8+ inculture stimulated with epimastigote antigens of the Col strain. The resultsare expressed as index ± standard error. Significant differences at p < 0.05are indicated by letters a, b and c for comparisons with days 9, 60 and 90,respectively. #: differences between the non-infected group (NI) and infectedgroups (Y or Col).

Mentions: Each strain favours distinct cytokine profiles - Stimulation of NIgroups with Y and Col strain epimastigote antigens did not yield any significantcytokine responses, indicating that the antigen was not able to stimulate the productionof IFN-γ or IL-4 by CD4+ and CD8+ T-lymphocytes in NI dogs. Incultures stimulated with the Y antigen, the production o IFN-γ by CD4+ Tlymphocytes was higher at 60 and 240 d.a.i. compared to 9 d.a.i. (Fig. 3A) and the production of IFN-γ by CD8+ Tlymphocytes was higher at 240 d.a.i. compared to the NI group at this same time pointand to that at 9 and 60 d.a.i. (Fig. 3C). IL-4production by CD8+ T lymphocytes increased in cultures stimulated with the Ystrain at 240 d.a.i. compared to 9 and 90 d.a.i. and in comparison with the NI group(Fig. 3D). In cultures stimulated with the Colantigen, IL-4 production was favoured by CD8+ T lymphocytes in comparisonwith the NI group at 90 d.a.i. (Fig. 3H).


The TcI and TcII Trypanosoma cruzi experimental infections induce distinct immune responses and cardiac fibrosis in dogs.

Duz AL, Vieira PM, Roatt BM, Aguiar-Soares RD, Cardoso JM, Oliveira FC, Reis LE, Tafuri WL, Veloso VM, Reis AB, Carneiro CM - Mem. Inst. Oswaldo Cruz (2014)

: immunophenotypic profile and cytokine patterns [interferon (INF)-γ andinterleukin (IL)-4] of CD4+ and CD8+ T-lymphocyte present in peripheral bloodbefore infection (0), nine, 60, 90 and 240 days after infection with Y strain(Y) or Colombian strain (Col) of Trypanosoma cruzi. T-cellssubsets were identified by flow cytometric immunostaining as described inMaterials and Methods. Data were expressed as the index, i.e., the meanpercentage of positive cells of cultures stimulated/mean percentage of positivecells of unstimulated cultures, within gated lymphocytes. A-D: index ofcytokine production by CD4+ or CD8+ in culture stimulated with epimastigoteantigens of the Y strain; E-H: index of cytokine production by CD4+ or CD8+ inculture stimulated with epimastigote antigens of the Col strain. The resultsare expressed as index ± standard error. Significant differences at p < 0.05are indicated by letters a, b and c for comparisons with days 9, 60 and 90,respectively. #: differences between the non-infected group (NI) and infectedgroups (Y or Col).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325618&req=5

f03: : immunophenotypic profile and cytokine patterns [interferon (INF)-γ andinterleukin (IL)-4] of CD4+ and CD8+ T-lymphocyte present in peripheral bloodbefore infection (0), nine, 60, 90 and 240 days after infection with Y strain(Y) or Colombian strain (Col) of Trypanosoma cruzi. T-cellssubsets were identified by flow cytometric immunostaining as described inMaterials and Methods. Data were expressed as the index, i.e., the meanpercentage of positive cells of cultures stimulated/mean percentage of positivecells of unstimulated cultures, within gated lymphocytes. A-D: index ofcytokine production by CD4+ or CD8+ in culture stimulated with epimastigoteantigens of the Y strain; E-H: index of cytokine production by CD4+ or CD8+ inculture stimulated with epimastigote antigens of the Col strain. The resultsare expressed as index ± standard error. Significant differences at p < 0.05are indicated by letters a, b and c for comparisons with days 9, 60 and 90,respectively. #: differences between the non-infected group (NI) and infectedgroups (Y or Col).
Mentions: Each strain favours distinct cytokine profiles - Stimulation of NIgroups with Y and Col strain epimastigote antigens did not yield any significantcytokine responses, indicating that the antigen was not able to stimulate the productionof IFN-γ or IL-4 by CD4+ and CD8+ T-lymphocytes in NI dogs. Incultures stimulated with the Y antigen, the production o IFN-γ by CD4+ Tlymphocytes was higher at 60 and 240 d.a.i. compared to 9 d.a.i. (Fig. 3A) and the production of IFN-γ by CD8+ Tlymphocytes was higher at 240 d.a.i. compared to the NI group at this same time pointand to that at 9 and 60 d.a.i. (Fig. 3C). IL-4production by CD8+ T lymphocytes increased in cultures stimulated with the Ystrain at 240 d.a.i. compared to 9 and 90 d.a.i. and in comparison with the NI group(Fig. 3D). In cultures stimulated with the Colantigen, IL-4 production was favoured by CD8+ T lymphocytes in comparisonwith the NI group at 90 d.a.i. (Fig. 3H).

Bottom Line: In addition, CD8+ T-lymphocytes isolated from the peripheral blood produced higher levels of interleukin (IL)-4.In the chronic phase, a significant increase in the number of inflammatory cells was detected in the right atrium.In the chronic phase, significant heart inflammation and fibrosis were observed, demonstrating that strains of different DTUs interact differently with the host.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunopatologia, Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil.

ABSTRACT
Trypanosoma cruzi infection may be caused by different strains with distinct discrete typing units (DTUs) that can result in variable clinical forms of chronic Chagas disease. The present study evaluates the immune response and cardiac lesions in dogs experimentally infected with different T. cruzi strains with distinct DTUs, namely, the Colombian (Col) and Y strains of TcI and TcII DTU, respectively. During infection with the Col strain, increased levels of alanine aminotransferase, erythrocytes, haematocrit and haemoglobin were observed. In addition, CD8+ T-lymphocytes isolated from the peripheral blood produced higher levels of interleukin (IL)-4. The latter suggests that during the acute phase, infection with the Col strain may remain unnoticed by circulating mononuclear cells. In the chronic phase, a significant increase in the number of inflammatory cells was detected in the right atrium. Conversely, infection with the Y strain led to leucopoenia, thrombopoenia, inversion of the ratio of CD4+/CD8+ T-lymphocytes and alterations in monocyte number. The Y strain stimulated the production of interferon-γ by CD4+ and CD8+ T-lymphocytes and IL-4 by CD8+ T-cells. In the chronic phase, significant heart inflammation and fibrosis were observed, demonstrating that strains of different DTUs interact differently with the host.

Show MeSH
Related in: MedlinePlus