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

Abstract

Doc number: 123

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.