title: 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: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, CPqRR-FIOCRUZ, Belo Horizonte, MG, Brazil. avelar@cpqrr.fiocruz.br
authors.forename: Renato
authors.initials: R
authors.lastname: Sathler-Avelar
authors.forename: Danielle Marquete
authors.initials: DM
authors.lastname: Vitelli-Avelar
authors.forename: Silvana Maria
authors.initials: SM
authors.lastname: Elói-Santos
authors.forename: Eliane Dias
authors.initials: ED
authors.lastname: Gontijo
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
mesh_terms: D000293:Adolescent; D000328:Adult; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000008:administration & dosage*; D018417:Th1 Cells / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*; D055815:Young Adult
chemical_list: D000981:Antiprotozoal Agents; D016207:Cytokines; D009593:Nitroimidazoles; C009999:benzonidazole