Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/32941
Title: Systems Biology Reveals Relevant Gaps in Fc-γR Expression, Impaired Regulatory Cytokine Microenvironment Interfaced With Anti-Trypanosoma cruzi IgG Reactivity in Cardiac Chagas Disease Patients
Authors: Gomes, Juliana de Assis Silva
Araújo, Fernanda Fortes de
Avelar, Daniele Marquete Vitelli
Avelar, Renato Sathler
Lage, Paula Souza
Wendling, Ana Paula Barbosa
Vale, Isabela Natalia Pascoal Campos do
Dias, João Carlo Pinto
Santos, Silvana Maria Elói
Carvalho, Andréa Teixeira de
Martins Filho, Olindo Assis
Affilliation: Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Laboratório de Biologia das Interações Celulares. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil / Universidade de Uberaba. Programa de Pós-graduação em Sanidade e Produção Animal nos Trópicos. Uberaba, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Triatomíneos. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Propedêutica Complementar. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil.
Abstract: The systems biology approach has become an innovative tool when it comes to shedding light on the complex immune response underlying the development/maintenance of distinct clinical forms of Chagas disease. The goal of this study was to describe an integrative overview of Fc-γR expression, cytokine microenvironment and anti-Trypanosoma cruzi IgG interface in indeterminate-(IND) and cardiac-(CARD) patients. Data demonstrated that IND displayed an overall higher Fcγ-R expression (CD16; CD32; CD64) on neutrophils-(NEU), along with (CD16; CD64) on monocytes-(MON) as compared to CARD. Additionally, CARD presented an increased expression of CD32 in B-cells. While preserved frequency of IL-10-producing cells was observed in IND, decreased levels of IL-10+ phagocytes and enhanced TNF+ MON and NK-cells were observed in CARD. T. cruzi-antigen recall in vitro induces a general decrease of Fc-γR expression in Chagas disease patients, especially in CARD. Moreover, T. cruzi-antigen stimuli triggered a concomitant increase of IFN-γ+NEU/TNF+NK-cells and IL-10+MON/IL-10+B-cells in IND. Biomarker signatures further emphasized the contrasting Fc-γR expression and cytokine microenvironment observed in Chagas disease patients with distinct clinical forms. Up-regulation of Fc-γR expression (CD16 on NEU;MON;NK) was observed in IND, whereas a general decrease was reported for CARD. Moreover, while a mixed cytokine microenvironment (TNF; IL-10) was observed in IND, CARD presented a contrasting profile with up-regulation of TNF+NEU and IL-12+NEU. Integrative network analysis revealed a distinct assemblage of biomarkers, with CARD presenting a large number of negative internode connectivity in comparison with IND. The relevant gaps in Fc-γR expression and impaired regulatory cytokine microenvironment interfaced with the anti-T. cruzi IgG reactivity throughout an exacerbated negative connectivity may account for the development/maintenance of the clinical status of cardiac Chagas disease.
Keywords: Chagas disease
Fc receptors
Trypanosoma cruzi
Cytokines
Immune response
keywords: Doença de Chagas
Receptores Fc
Trypanosoma cruzi
Citocinas
Resposta imune
Issue Date: 2018
Publisher: Frontiers Research Foundation
Citation: GOMES, Juliana de Assis Silva et al. Systems Biology Reveals Relevant Gaps in Fc-γR Expression, Impaired Regulatory Cytokine Microenvironment Interfaced With Anti-Trypanosoma cruzi IgG Reactivity in Cardiac Chagas Disease Patients. Frontiers in Microbiology, v. 9, p. 1-10, 2018.
DOI: 10.3389/fmicb.2018.01608. eCollection 2018
ISSN: 1664-302X
Copyright: open access
Appears in Collections:MG - IRR - Artigos de Periódicos

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