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Open Access Research article

Blood leukocytes from benznidazole-treated indeterminate chagas disease patients display an overall type-1-modulated cytokine profile upon short-term in vitro stimulation with trypanosoma cruzi antigens

Renato Sathler-Avelar12356*, Danielle Marquete Vitelli-Avelar15, Silvana Maria Elói-Santos45, Eliane Dias Gontijo45, Andréa Teixeira-Carvalho15 and Olindo Assis Martins-Filho15

Author Affiliations

1 Laboratório de Biomarcadores de Diagnóstico e Monitoração, CPqRR-FIOCRUZ, Belo Horizonte, MG, Brazil

2 Unicentro Newton Paiva, Belo Horizonte, MG, Brazil

3 Universidade Vale do Rio Verde, UninCor, Belo Horizonte, MG, Brazil

4 Departamento de Medicina Preventiva e Social, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

5 Departamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

6 Laboratório de Biomarcadores de Diagnóstico e Monitoração, R, Laboratório de Biomarcadores de Diagnóstico e Monitoração, CPqRR-FIOCRUZ, Av. Augusto de Lima 1715, 30190–002, Belo Horizonte, MG, Brazil

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BMC Infectious Diseases 2012, 12:123  doi:10.1186/1471-2334-12-123

Published: 24 May 2012

Abstract

Background

Benznidazole (Bz)-chemotherapy is recommended to prevent Chagas disease progression, despite its limited efficacy during chronic disease. However, the host mechanisms underlying these benefits still remain to be elucidated.

Methods

In this study, we have used short-term whole blood cultures to describe the cytokine profile of Bz-treated Indeterminate Chagas disease patients-(INDt) as compared to untreated patients-(IND).

Results

Our findings showed that IND presented increased levels of IL-10+neutrophils, IL-12+ and IL-10+monocytes and IFN-γ+NK-cells. Moreover, IND showed slight increase of IL-4+CD4+T-cells and enhanced levels of IL-10+CD8+T-cells and B-cells. Additional analysis of cytokine Low and High producers also highlighted the presence of High cytokine producers within IND, including IL-10 from CD4+ T-cells and IFN-γ from CD8+ T-cells, as compared to NI. The Bz-treatment lead to an overall cytokine down-regulation in the innate and adaptive compartments, including low levels of IL-12+ and IL-10+neutrophils and monocytes, IFN-γ+NK-cells, IL-12+, TNF-α+, IFN-γ+ and IL-5+CD4+T-cells and IL-10+B-cells, along with basal levels of cytokine-expressing CD8+T-cells in INDt as compared to IND. The in vitro antigen stimulation shifted the cytokine profile toward a type 1-modulated profile, with increased levels of IL-12+ and IL-10+ monocytes, IFN-γ+ and IL-4+NK-cells along with TNF-α+ and IFN-γ+CD8+T-cells. Analysis of Low and High cytokine producers, upon in vitro antigen stimulation, further confirm these data.

Conclusion

Together, our findings showed that the Bz treatment of Indeterminate Chagas’ disease patients shifts the cytokine patterns of peripheral blood monocytes, NK-cells and CD8+ T-cells towards a long-lasting Type-1-modulated profile that could be important to the maintenance of a non-deleterious immunological microenvironment.

Keywords:
Chagas disease; Benznidazole; Immune response; Cytokines; Leucocytes subsets; CNPq; FAPEMIG; FIOCRUZ