title: Etiological treatment of Chagas disease patients with benznidazole lead to a sustained pro-inflammatory profile counterbalanced by modulatory events.
abstract: In the present study, we characterized the phagocytic capacity, cytokine profile along with the FCγ-R and TLR expression in leukocytes from Chagas disease patients (indeterminate-IND and cardiac-CARD) before and one-year after Bz-treatment (INDT and CARDT). A down-regulation of IL-17, IFN-γ and IL-10 synthesis by neutrophils was observed in CARDT. The Bz-treatment did not impact on the expression of phagocytosis-related surface molecules or monocyte-derived cytokine profile in INDT. Although CARDT showed unaltered monocyte-phagocytic capacity, up-regulated expression of Fcγ-RI/III and TLR-4 may be related to their ability to produce IL-10 and TGF-β. Down-regulation of lymphocyte-derived cytokine was observed in INDT whereas up-regulated cytokine profile was observed for lymphocytes in CARDT. Analysis of cytokine network revealed that IND displayed a multifaceted cytokine response characterized by strong connecting axes involving pro-inflammatory/regulatory phagocytes and lymphocytes. On the other hand, CARD presented a modest cytokine network. The Bz-treatment leads to distinct cytokine network: decreasing the links in INDT, with a pivotal role of IL-10(+) monocytes and expanding the connections in CARDT. Our findings highlighted that the Bz-treatment contributes to an overall immunomodulation in INDT and induces a broad change of immunological response in CARDT, eliciting an intricate phenotypic/functional network compatible with beneficial and protective immunological events.
authors: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil.
authors: A C
authors: AC
authors: Campi-Azevedo
authors: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil; Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil; Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil; Programa de Pós- graduação em Medicina Tropical e Infectologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil. Electronic address: juliana@icb.ufmg.br.
authors: J A S
authors: JA
authors: Gomes
authors: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil.
authors: A
authors: A
authors: Teixeira-Carvalho
authors: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil.
authors: D
authors: D
authors: Silveira-Lemos
authors: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil.
authors: D M
authors: DM
authors: Vitelli-Avelar
authors: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil.
authors: R
authors: R
authors: Sathler-Avelar
authors: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil.
authors: V
authors: V
authors: Peruhype-Magalhães
authors: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil.
authors: S R
authors: SR
authors: Béla
authors: Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
authors: K F
authors: KF
authors: Silvestre
authors: Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
authors: M A
authors: MA
authors: Batista
authors: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil.
authors: N C C
authors: NC
authors: Schachnik
authors: Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais - INCT-DT, Brasil.
authors: R
authors: R
authors: Correa-Oliveira
authors: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil.
authors: S M
authors: SM
authors: Eloi-Santos
authors: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brasil.
authors: O A
authors: OA
authors: Martins-Filho
mesh_terms: D000293:Adolescent; D000328:Adult; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology; D065187:Controlled Before-After Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D056747:Immunomodulation; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D009593:Nitroimidazoles / Q000008:administration & dosage*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014344:Trypanocidal Agents / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D016207:Cytokines; C489017:FCGR1A protein, human; C496124:FCGR3A protein, human; D018836:Inflammation Mediators; D009593:Nitroimidazoles; D017452:Receptors, IgG; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014344:Trypanocidal Agents; C009999:benzonidazole
keywords: Benznidazole treatment; Chagas disease; Cytokine profile; FCγ-R; Phagocytic capacity; TLR expression