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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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: ex-vivo quantification of CD4+ (A) and CD8+ T lymphocytes (B), B+lymphocytes (C) and CD14+ monocytes (D) before infection (0) and nine, 30, 60and 240 days after infection with Y strain (Y) or Colombian strain (Col) ofTrypanosoma cruzi. The cell subsets were identified by flowcytometric immunostaining as described in Materials and Methods. Results areexpressed as absolute cell counts in scatter plots ± standard error.Significant differences at p < 0.05 are indicated by letters a, b, c and dfor comparisons with days 0, 9, 60 and 240, respectively. #: differencesbetween the non-infected group (NI) and infected groups (Y or Col); *:differences between Y and Col groups at each time point.
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f02: : ex-vivo quantification of CD4+ (A) and CD8+ T lymphocytes (B), B+lymphocytes (C) and CD14+ monocytes (D) before infection (0) and nine, 30, 60and 240 days after infection with Y strain (Y) or Colombian strain (Col) ofTrypanosoma cruzi. The cell subsets were identified by flowcytometric immunostaining as described in Materials and Methods. Results areexpressed as absolute cell counts in scatter plots ± standard error.Significant differences at p < 0.05 are indicated by letters a, b, c and dfor comparisons with days 0, 9, 60 and 240, respectively. #: differencesbetween the non-infected group (NI) and infected groups (Y or Col); *:differences between Y and Col groups at each time point.

Mentions: Haematological alterations resulting from T. cruzi infection - Whenanalysing the haematological alterations, it was observed that the erythrocyte andhaematocrit levels were increased in the Col group at 30, 90 and 240 d.a.i. compared today 0. Haemoglobin was increased at 240 d.a.i. compared to day 0 for the NI and Ygroups. In the Col group, this increase was observed at 30 and 240 d.a.i. compared today 0. Platelets were decreased at 9 d.a.i. compared to day 0 in the Y group(Supplementary data, Table I). Infection with the Y strain resulted in leucopoenia at 9d.a.i. compared to day 0. A reduction in peripheral blood monocytes was observed at nineand 240 d.a.i. with the Y strain compared to day 0, whereas this was observed at 90d.a.i. for the Col group (Supplementary data, Table II). Y strain infection alteredperipheral blood leucocytes in ex vivo analysis; T-lymphocyte CD4+ levelswere reduced at 9 d.a.i. with the Y strain compared to day 0, 60 and 240 d.a.i. (Fig. 2A). T-lymphocyte CD8+ cells of the Ystrain-infected group increased at 30 d.a.i. compared to day 0 and 9 d.a.i. andincreased in comparison with the NI and Col groups at the same experimental time points(Fig. 2B). In terms of CD4+ andCD8+ T lymphocyte ratios, a reduction was observed during Y infection at30 d.a.i. compared to the non-infected group (data not shown). The B+lymphocyte frequency dropped dramatically between day 0-9 d.a.i. with the Y strain andremained constant throughout the rest of the experiment, whereas in the case ofinfection with the Col strain, the decrease in B+ lymphocytes was progressivefrom day 0-30 d.a.i. (Fig. 2C). CD14+monocyte frequencies were highly variable and were drastically lower at 9 d.a.i.compared to day 0 in the Y group, but this percentage was higher at 30 d.a.i. (Fig. 2D).


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)

: ex-vivo quantification of CD4+ (A) and CD8+ T lymphocytes (B), B+lymphocytes (C) and CD14+ monocytes (D) before infection (0) and nine, 30, 60and 240 days after infection with Y strain (Y) or Colombian strain (Col) ofTrypanosoma cruzi. The cell subsets were identified by flowcytometric immunostaining as described in Materials and Methods. Results areexpressed as absolute cell counts in scatter plots ± standard error.Significant differences at p < 0.05 are indicated by letters a, b, c and dfor comparisons with days 0, 9, 60 and 240, respectively. #: differencesbetween the non-infected group (NI) and infected groups (Y or Col); *:differences between Y and Col groups at each time point.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f02: : ex-vivo quantification of CD4+ (A) and CD8+ T lymphocytes (B), B+lymphocytes (C) and CD14+ monocytes (D) before infection (0) and nine, 30, 60and 240 days after infection with Y strain (Y) or Colombian strain (Col) ofTrypanosoma cruzi. The cell subsets were identified by flowcytometric immunostaining as described in Materials and Methods. Results areexpressed as absolute cell counts in scatter plots ± standard error.Significant differences at p < 0.05 are indicated by letters a, b, c and dfor comparisons with days 0, 9, 60 and 240, respectively. #: differencesbetween the non-infected group (NI) and infected groups (Y or Col); *:differences between Y and Col groups at each time point.
Mentions: Haematological alterations resulting from T. cruzi infection - Whenanalysing the haematological alterations, it was observed that the erythrocyte andhaematocrit levels were increased in the Col group at 30, 90 and 240 d.a.i. compared today 0. Haemoglobin was increased at 240 d.a.i. compared to day 0 for the NI and Ygroups. In the Col group, this increase was observed at 30 and 240 d.a.i. compared today 0. Platelets were decreased at 9 d.a.i. compared to day 0 in the Y group(Supplementary data, Table I). Infection with the Y strain resulted in leucopoenia at 9d.a.i. compared to day 0. A reduction in peripheral blood monocytes was observed at nineand 240 d.a.i. with the Y strain compared to day 0, whereas this was observed at 90d.a.i. for the Col group (Supplementary data, Table II). Y strain infection alteredperipheral blood leucocytes in ex vivo analysis; T-lymphocyte CD4+ levelswere reduced at 9 d.a.i. with the Y strain compared to day 0, 60 and 240 d.a.i. (Fig. 2A). T-lymphocyte CD8+ cells of the Ystrain-infected group increased at 30 d.a.i. compared to day 0 and 9 d.a.i. andincreased in comparison with the NI and Col groups at the same experimental time points(Fig. 2B). In terms of CD4+ andCD8+ T lymphocyte ratios, a reduction was observed during Y infection at30 d.a.i. compared to the non-infected group (data not shown). The B+lymphocyte frequency dropped dramatically between day 0-9 d.a.i. with the Y strain andremained constant throughout the rest of the experiment, whereas in the case ofinfection with the Col strain, the decrease in B+ lymphocytes was progressivefrom day 0-30 d.a.i. (Fig. 2C). CD14+monocyte frequencies were highly variable and were drastically lower at 9 d.a.i.compared to day 0 in the Y group, but this percentage was higher at 30 d.a.i. (Fig. 2D).

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