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AutorAvelar, Danielle Marquete Vitelli
AutorAvelar, Renato Sathler
AutorBarbosa, Armanda Moreira Mattoso
AutorGouin, Nicolas
AutorOliveira, Marcelo Perdigão de
AutorReis, Leydiane Valério dos
AutorCosta, Ronaldo Peres
AutorSantos, Silvana Maria Elói
AutorGomes, Matheus de Souza
AutorAmaral, Laurence Rodrigues do
AutorCarvalho, Andréa Teixeira de
AutorMartins Filho, Olindo Assis
AutorDick Jr., Edward J.
AutorHubbard, Gene B.
AutorVandeBerg, Jane F.
AutorVandeBerg, John L.
Fecha de acceso2018-05-24T15:51:41Z
Fecha de disponibilización2018-05-24T15:51:41Z
Fecha de publicación2017
ReferenciaAVELAR, Danielle Marquete Vitelli et al. Cynomolgus macaques naturally infected with Trypanosoma cruzi-I exhibit an overall mixed pro-inflammatory/modulated cytokine signature characteristic of human Chagas disease. PLoS Negl Trop Dis., v. 11, n. 2, e0005233, 2017.pt_BR
ISSN1935-2727pt_BR
URIhttps://www.arca.fiocruz.br/handle/icict/26634
Idiomaengpt_BR
EditorPublic Library of Sciencept_BR
Derechos de autorrestricted accesspt_BR
Palabras clave en Portuguéscitocinaspt_BR
Palabras clave en Portuguésmacacopt_BR
Palabras clave en PortuguésTrypanosoma cruzipt_BR
Palabras clave en Portuguésdoença de chagaspt_BR
TítuloCynomolgus macaques naturally infected with Trypanosoma cruzi-I exhibit an overall mixed pro-inflammatory/modulated cytokine signature characteristic of human Chagas disease.pt_BR
Tipo del documentoArticle
DOI10.1371/journal.pntd.0005233
Resumen en InglésBackground: Non-human primates have been shown to be useful models for Chagas disease. We previously reported that natural T. cruzi infection of cynomolgus macaques triggers clinical features and immunophenotypic changes of peripheral blood leukocytes resembling those observed in human Chagas disease. In the present study, we further characterize the cytokine-mediated microenvironment to provide supportive evidence of the utility of cynomolgus macaques as a model for drug development for human Chagas disease. Methods and findings: In this cross-sectional study design, flow cytometry and systems biology approaches were used to characterize the ex vivo and in vitro T. cruzi-specific functional cytokine signature of circulating leukocytes from TcI-T. cruzi naturally infected cynomolgus macaques (CH). Results showed that CH presented an overall CD4+-derived IFN-γ pattern regulated by IL-10-derived from CD4+ T-cells and B-cells, contrasting with the baseline profile observed in non-infected hosts (NI). Homologous TcI-T. cruzi-antigen recall in vitro induced a broad pro-inflammatory cytokine response in CH, mediated by TNF from innate/adaptive cells, counterbalanced by monocyte/B-cell-derived IL-10. TcIV-antigen triggered a more selective cytokine signature mediated by NK and T-cell-derived IFN-γ with modest regulation by IL-10 from T-cells. While NI presented a cytokine network comprised of small number of neighborhood connections, CH displayed a complex cross-talk amongst network elements. Noteworthy, was the ability of TcI-antigen to drive a complex global pro-inflammatory network mediated by TNF and IFN-γ from NK-cells, CD4+ and CD8+ T-cells, regulated by IL-10+CD8+ T-cells, in contrast to the TcIV-antigens that trigger a modest network, with moderate connecting edges. Conclusions: Altogether, our findings demonstrated that CH present a pro-inflammatory/regulatory cytokine signature similar to that observed in human Chagas disease. These data bring additional insights that further validate these non-human primates as experimental models for Chagas disease.pt_BR
AfiliaciónGrupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, MG, Brazil/Southwest National Primates Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States of Americapt_BR
AfiliaciónGrupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, MG, Brazil/Southwest National Primates Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States of America/Centro Universitário Newton Paiva, Belo Horizonte, MG, Brazil/Faculdade de Minas. Belo Horizonte, MG, Brazilpt_BR
AfiliaciónGrupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, MG, Brazil/Centro Universitário Newton Paiva, Belo Horizonte, MG, Brazil/ Faculdade de Minas. Belo Horizonte, MG, Brazilpt_BR
AfiliaciónUniversidad de La Serena. La Serena, Chilept_BR
AfiliaciónFundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil/ Centro Universitário Newton Paiva. Belo Horizonte, MG, Brazilpt_BR
AfiliaciónFundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil/ Centro Universitário Newton Paiva. Belo Horizonte, MG, Brazilpt_BR
AfiliaciónCentro Universitário Newton Paiva. Belo Horizonte, MG, Brazilpt_BR
AfiliaciónFundação 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, Brazilpt_BR
AfiliaciónUniversidade Federal de Uberlândia. Faculdade de Ciência da Computação. Laboratório de Bioinformática e Análise Molecular. Patos de Minas, MG, Brazilpt_BR
AfiliaciónUniversidade Federal de Uberlândia. Faculdade de Ciência da Computação. Laboratório de Bioinformática e Análise Molecular. Patos de Minas, MG, Brazilpt_BR
AfiliaciónFundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazilpt_BR
AfiliaciónFundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazilpt_BR
AfiliaciónSouthwest National Primates Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States of Americapt_BR
AfiliaciónSouthwest National Primates Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States of Americapt_BR
AfiliaciónSouthwest National Primates Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States of America/South Texas Diabetes and Obesity Institute. School of Medicine. University of Texas Rio Grande Valley, Brownsville/Harlingen/Edinburg, TX, United States of Americapt_BR
AfiliaciónSouthwest National Primates Research Center. Texas Biomedical Research Institute. San Antonio, TX, United States of America/South Texas Diabetes and Obesity Institute. School of Medicine. University of Texas Rio Grande Valley, Brownsville/Harlingen/Edinburg, TX, United States of Americapt_BR
Palavras clave en InglêsCytokinespt_BR
Palavras clave en InglêsMacaquept_BR
Palavras clave en InglêsTrypanosoma cruzipt_BR
Palavras clave en InglêsChagas diseasept_BR
Palavras clave en InglêsT cellspt_BR
Palavras clave en InglêsWhite blood cellspt_BR
Palavras clave en InglêsPrimatespt_BR
Palavras clave en InglêsImmune responsept_BR
Fecha de embargo2022-01-01
xmlui.metadata.dc.subject.ods03 Saúde e Bem-Estar


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