Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/14852 |
Resumo: | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, Minas Gerais, Brazil/Centro Universitário Newton Paiva. Belo Horizonte, MG, Brasil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, Brasil/Texas Biomedical Research Institute. San Antonio, TX, United States of America |
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Avelar, Renato SathlerAvelar, Danielle Marquete VitelliBarbosa, Armanda Moreira MattosoOliveira, Marcelo Perdigão deCosta, Ronaldo PeresSantos, Silvana Maria ElóiGomes, Matheus de SouzaAmaral, Laurence Rodrigues doCarvalho, Andréa Teixeira deMartins Filho, Olindo AssisDick Junior, Edward J.Hubbard, Gene B.VandeBerg, Jane F.VandeBerg, John L.2016-07-13T16:45:28Z2016-07-13T16:45:28Z2016AVELAR, Renato Sathler et al. Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease. PLoS Negl Trop Dis. Vol. 10, n. 1, p. e0004302, 2016.1935-2735https://www.arca.fiocruz.br/handle/icict/1485210.1371/journal.pntd.0004302. eCollection 2016engPublic Library of SciencePhenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Diseaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, Minas Gerais, Brazil/Centro Universitário Newton Paiva. Belo Horizonte, MG, Brasil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, Brasil/Texas Biomedical Research Institute. San Antonio, TX, United States of AmericaFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, Minas Gerais, Brazil/Texas Biomedical Research Institute. San Antonio, TX, United States of America/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, Minas Gerais, Brazil/Centro Universitário Newton Paiva. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, Minas Gerais, Brazil/Centro Universitário Newton Paiva. Belo Horizonte, MG, BrasilCentro Universitário Newton Paiva. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Propedêutica Complementar. Belo Horizonte, MG, BrasilLaboratório de Bioinformática e Análise Molecular, Instituto de Genética e Bioquímica Universidade Federal de Uberlândia, Campus Patos de Minas, Patos de Minas, Minas Gerais, BrazilUniversidade Federal de Uberlândia. Faculdade de Ciência da Computação. Laboratório de Bioinformática e Análise Molecular. Patos de Minas, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, Minas Gerais, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, Minas Gerais, BrasilTexas Biomedical Research Institute. San Antonio, TX, United States of AmericaTexas Biomedical Research Institute. San Antonio, TX, United States of AmericaTexas Biomedical Research Institute. San Antonio, TX, United States of America/University of Texas Health Science Center. South Texas Diabetes and Obesity Institute. San Antonio – Regional Academic Health Center. Edinburg, TX, United States of AmericaTexas Biomedical Research Institute. San Antonio, TX, United States of America/University of Texas Health Science Center. South Texas Diabetes and Obesity Institute. San Antonio – Regional Academic Health Center. Edinburg, TX, United States of AmericaBACKGROUND: Cynomolgus macaques (Macaca fascicularis) represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. We have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus macaques naturally infected with T. cruzi (CH) presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations. METHODS AND FINDINGS: Our data established that CH displayed increased expression of CD32+ and CD56+ in monocytes and enhanced frequency of NK Granzyme A+ cells as compared to non-infected controls (NI). Moreover, higher expression of CD54 and HLA-DR by T-cells, especially within the CD8+ subset, was the hallmark of CH. A high level of expression of Granzyme A and Perforin underscored the enhanced cytotoxicity-linked pattern of CD8+ T-lymphocytes from CH. Increased frequency of B-cells with up-regulated expression of Fc-γRII was also observed in CH. Complex and imbricate biomarker networks demonstrated that CH showed a shift towards cross-talk among cells of the adaptive immune system. Systems biology analysis further established monocytes and NK-cell phenotypes and the T-cell activation status, along with the Granzyme A expression by CD8+ T-cells, as the most reliable biomarkers of potential use for clinical applications. CONCLUSIONS: Altogether, these findings demonstrated that the similarities in phenotypic features of circulating leukocytes observed in cynomolgus macaques and humans infected with T. cruzi further supports the use of these monkeys in preclinical toxicology and pharmacology studies applied to development and testing of new drugs for Chagas disease.B-Lymphocytes/immunologyCD8-Positive T-Lymphocytes/immunologyChagas Disease/immunologyChagas Disease/parasitologyDisease Models, AnimalKiller Cells, Natural/immunologyTrypanosoma cruzi/physiologyinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv |
Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease |
title |
Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease |
spellingShingle |
Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease Avelar, Renato Sathler B-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology Chagas Disease/immunology Chagas Disease/parasitology Disease Models, Animal Killer Cells, Natural/immunology Trypanosoma cruzi/physiology |
title_short |
Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease |
title_full |
Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease |
title_fullStr |
Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease |
title_full_unstemmed |
Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease |
title_sort |
Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease |
author |
Avelar, Renato Sathler |
author_facet |
Avelar, Renato Sathler Avelar, Danielle Marquete Vitelli Barbosa, Armanda Moreira Mattoso Oliveira, Marcelo Perdigão de Costa, Ronaldo Peres Santos, Silvana Maria Elói Gomes, Matheus de Souza Amaral, Laurence Rodrigues do Carvalho, Andréa Teixeira de Martins Filho, Olindo Assis Dick Junior, Edward J. Hubbard, Gene B. VandeBerg, Jane F. VandeBerg, John L. |
author_role |
author |
author2 |
Avelar, Danielle Marquete Vitelli Barbosa, Armanda Moreira Mattoso Oliveira, Marcelo Perdigão de Costa, Ronaldo Peres Santos, Silvana Maria Elói Gomes, Matheus de Souza Amaral, Laurence Rodrigues do Carvalho, Andréa Teixeira de Martins Filho, Olindo Assis Dick Junior, Edward J. Hubbard, Gene B. VandeBerg, Jane F. VandeBerg, John L. |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Avelar, Renato Sathler Avelar, Danielle Marquete Vitelli Barbosa, Armanda Moreira Mattoso Oliveira, Marcelo Perdigão de Costa, Ronaldo Peres Santos, Silvana Maria Elói Gomes, Matheus de Souza Amaral, Laurence Rodrigues do Carvalho, Andréa Teixeira de Martins Filho, Olindo Assis Dick Junior, Edward J. Hubbard, Gene B. VandeBerg, Jane F. VandeBerg, John L. |
dc.subject.en.pt_BR.fl_str_mv |
B-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology Chagas Disease/immunology Chagas Disease/parasitology Disease Models, Animal Killer Cells, Natural/immunology Trypanosoma cruzi/physiology |
topic |
B-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology Chagas Disease/immunology Chagas Disease/parasitology Disease Models, Animal Killer Cells, Natural/immunology Trypanosoma cruzi/physiology |
description |
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, Minas Gerais, Brazil/Centro Universitário Newton Paiva. Belo Horizonte, MG, Brasil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, Brasil/Texas Biomedical Research Institute. San Antonio, TX, United States of America |
publishDate |
2016 |
dc.date.accessioned.fl_str_mv |
2016-07-13T16:45:28Z |
dc.date.available.fl_str_mv |
2016-07-13T16:45:28Z |
dc.date.issued.fl_str_mv |
2016 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
AVELAR, Renato Sathler et al. Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease. PLoS Negl Trop Dis. Vol. 10, n. 1, p. e0004302, 2016. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/14852 |
dc.identifier.issn.pt_BR.fl_str_mv |
1935-2735 |
dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pntd.0004302. eCollection 2016 |
identifier_str_mv |
AVELAR, Renato Sathler et al. Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease. PLoS Negl Trop Dis. Vol. 10, n. 1, p. e0004302, 2016. 1935-2735 10.1371/journal.pntd.0004302. eCollection 2016 |
url |
https://www.arca.fiocruz.br/handle/icict/14852 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Public Library of Science |
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Public Library of Science |
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