| Summary: | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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).</p> <p>Results</p> <p>Our findings showed that IND presented increased levels of IL-10<sup>+</sup>neutrophils, IL-12<sup>+</sup> and IL-10<sup>+</sup>monocytes and IFN-γ<sup>+</sup>NK-cells. Moreover, IND showed slight increase of IL-4<sup>+</sup>CD4<sup>+</sup>T-cells and enhanced levels of IL-10<sup>+</sup>CD8<sup>+</sup>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<sup>+</sup> 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<sup>+</sup> and IL-10<sup>+</sup>neutrophils and monocytes, IFN-γ<sup>+</sup>NK-cells, IL-12<sup>+</sup>, TNF-α<sup>+</sup>, IFN-γ<sup>+</sup> and IL-5<sup>+</sup>CD4<sup>+</sup>T-cells and IL-10<sup>+</sup>B-cells, along with basal levels of cytokine-expressing CD8<sup>+</sup>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<sup>+</sup> and IL-10<sup>+</sup> monocytes, IFN-γ<sup>+</sup> and IL-4<sup>+</sup>NK-cells along with TNF-α<sup>+</sup> and IFN-γ<sup>+</sup>CD8<sup>+</sup>T-cells. Analysis of Low and High cytokine producers, upon in vitro antigen stimulation, further confirm these data.</p> <p>Conclusion</p> <p>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<sup>+</sup> T-cells towards a long-lasting Type-1-modulated profile that could be important to the maintenance of a non-deleterious immunological microenvironment.</p>
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