Author | Avelar, Renato Sathler | |
Author | Avelar, Danielle Marquete Vitelli | |
Author | Barbosa, Armanda Moreira Mattoso | |
Author | Oliveira, Marcelo Perdigão de | |
Author | Costa, Ronaldo Peres | |
Author | Santos, Silvana Maria Elói | |
Author | Gomes, Matheus de Souza | |
Author | Amaral, Laurence Rodrigues do | |
Author | Carvalho, Andréa Teixeira de | |
Author | Martins Filho, Olindo Assis | |
Author | Dick Junior, Edward J. | |
Author | Hubbard, Gene B. | |
Author | VandeBerg, Jane F. | |
Author | VandeBerg, John L. | |
Access date | 2016-07-13T16:45:28Z | |
Available date | 2016-07-13T16:45:28Z | |
Document date | 2016 | |
Citation | 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. | pt_BR |
ISSN | 1935-2735 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/14852 | |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | pt_BR |
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 | pt_BR |
Type | Article | pt_BR |
DOI | 10.1371/journal.pntd.0004302. eCollection 2016 | |
Abstract | BACKGROUND: 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. | pt_BR |
Affilliation | 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 | pt_BR |
Affilliation | Fundação 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, Brasil | pt_BR |
Affilliation | 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 | pt_BR |
Affilliation | 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 | pt_BR |
Affilliation | Centro Universitário Newton Paiva. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Propedêutica Complementar. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Laboratório de Bioinformática e Análise Molecular, Instituto de Genética e Bioquímica Universidade Federal de Uberlândia, Campus Patos de Minas, Patos de Minas, Minas Gerais, Brazil | pt_BR |
Affilliation | Universidade Federal de Uberlândia. Faculdade de Ciência da Computação. Laboratório de Bioinformática e Análise Molecular. Patos de Minas, MG, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, Minas Gerais, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, Minas Gerais, Brasil | pt_BR |
Affilliation | Texas Biomedical Research Institute. San Antonio, TX, United States of America | pt_BR |
Affilliation | Texas Biomedical Research Institute. San Antonio, TX, United States of America | pt_BR |
Affilliation | Texas 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 America | pt_BR |
Affilliation | Texas 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 America | pt_BR |
Subject | B-Lymphocytes/immunology | pt_BR |
Subject | CD8-Positive T-Lymphocytes/immunology | pt_BR |
Subject | Chagas Disease/immunology | pt_BR |
Subject | Chagas Disease/parasitology | pt_BR |
Subject | Disease Models, Animal | pt_BR |
Subject | Killer Cells, Natural/immunology | pt_BR |
Subject | Trypanosoma cruzi/physiology | pt_BR |