title: Etiological treatment during early chronic indeterminate Chagas disease incites an activated status on innate and adaptive immunity associated with a type 1-modulated cytokine pattern.
abstract: Pro-inflammatory immune response is usually associated with Chagas disease pathogenesis, but is also relevant to treatment effectiveness. Cross-sectional studies have suggested that this activated state may persist for years after therapeutic intervention. However, short-term longitudinal investigation has suggested that the Benznidazole treatment (Bz-treatment) leads to decreased immunological activation. In order to elucidate this issue, we performed a longitudinal study to evaluate the immunological status following Bz-treatment during early indeterminate Chagas disease. Our results demonstrated that Bz-treatment led to higher activation status of circulating monocytes but was negatively associated with the number of IL-12(+)CD14(+) cells. Moreover, Bz-treatment triggered a high frequency of circulating CD3(-)CD16(+)CD56(-) NK cells, in addition to elevated activation status associated with a type 1-modulated cytokine pattern. Bz-treatment induced substantial T and B-cell activation status associated with an overall IL-10 modulated type 1 cytokine profile. In summary, these findings provide new information regarding immune activation status following the etiological treatment of Chagas disease. These results suggest that in addition to the increased number of activated leukocytes in the peripheral blood, Bz-treatment may also involve a qualitative change in their functional capacity that drives their activation state toward a modulated cytokine profile. These changes may account for the benefits of etiological treatment of Chagas disease.
authors.affiliation: Laboratory of Chagas Disease, CPqRR-FIOCRUZ, Av. Augusto de Lima 1715, 30190-002 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: Rodrigo Lima
authors.initials: RL
authors.lastname: Massara
authors.forename: Marta
authors.initials: M
authors.lastname: de Lana
authors.forename: João Carlos
authors.initials: JC
authors.lastname: Pinto Dias
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.forename: Silvana Maria
authors.initials: SM
authors.lastname: Elói-Santos
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology*; D002648:Child; D016207:Cytokines / Q000096:biosynthesis*; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology; D009593:Nitroimidazoles / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000981:Antiprotozoal Agents; D015415:Biomarkers; D016207:Cytokines; D009593:Nitroimidazoles; C009999:benzonidazole