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.
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.
  
  
  RESULTS
  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.
authors.affiliation: Grupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.|Centro Universitário Newton Paiva, Belo Horizonte, Minas Gerais, Brazil.|Pós-graduação em Patologia, Faculdade de Medicina, UFMG, Belo Horizonte, Minas Gerais, Brazil.|Texas Biomedical Research Institute, San Antonio, Texas, United States of America.
authors.forename: Renato
authors.initials: R
authors.lastname: Sathler-Avelar
authors.affiliation: Grupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.|Texas Biomedical Research Institute, San Antonio, Texas, United States of America.|Pós-graduação em Ciências da Saúde, Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Danielle Marquete
authors.initials: DM
authors.lastname: Vitelli-Avelar
authors.affiliation: Grupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.|Centro Universitário Newton Paiva, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Armanda Moreira
authors.initials: AM
authors.lastname: Mattoso-Barbosa
authors.affiliation: Grupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.|Centro Universitário Newton Paiva, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Perdigão-de-Oliveira
authors.affiliation: Centro Universitário Newton Paiva, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ronaldo Peres
authors.initials: RP
authors.lastname: Costa
authors.affiliation: Departamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Silvana Maria
authors.initials: SM
authors.lastname: Elói-Santos
authors.affiliation: 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.
authors.forename: Matheus de Souza
authors.initials: Mde S
authors.lastname: Gomes
authors.affiliation: Laboratório de Bioinformática e Análise Molecular, Faculdade de Ciência da Computação, Universidade Federal de Uberlândia, Campus Patos de Minas, Patos de Minas, Minas Gerais, Brazil.
authors.forename: Laurence Rodrigues do
authors.initials: LR
authors.lastname: Amaral
authors.affiliation: Grupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.affiliation: Grupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
authors.affiliation: Texas Biomedical Research Institute, San Antonio, Texas, United States of America.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Dick
authors.affiliation: Texas Biomedical Research Institute, San Antonio, Texas, United States of America.
authors.forename: Gene B
authors.initials: GB
authors.lastname: Hubbard
authors.affiliation: Texas Biomedical Research Institute, San Antonio, Texas, United States of America.|South Texas Diabetes and Obesity Institute, University of Texas Health Science Center, San Antonio - Regional Academic Health Center, Edinburg, Texas, United States of America.
authors.forename: Jane F
authors.initials: JF
authors.lastname: VandeBerg
authors.affiliation: Texas Biomedical Research Institute, San Antonio, Texas, United States of America.|South Texas Diabetes and Obesity Institute, University of Texas Health Science Center, San Antonio - Regional Academic Health Center, Edinburg, Texas, United States of America.
authors.forename: John L
authors.initials: JL
authors.lastname: VandeBerg
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D007962:Leukocytes / Q000276:immunology*; D008252:Macaca fascicularis / Q000276:immunology / Q000469:parasitology; D008297:Male; D009000:Monocytes / Q000276:immunology; D014349:Trypanosoma cruzi / Q000502:physiology*