Phenotypic features of circulating leukocytes from non-human primates naturally infected with trypanosoma cruzi resemble the major immunological findings observed in human chagas disease

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dc.creatorRenato Sathler-avelar
dc.creatorOlindo Assis Martins-filho
dc.creatorEdward j. Dick
dc.creatorGene b. Hubbard
dc.creatorJane f. Vandeberg
dc.creatorJohn l. Vandeberg
dc.creatorDanielle Marchetti Vitelli Avelar
dc.creatorArmanda Moreira Mattoso-barbosa
dc.creatorMarcelo Perdigão-de-oliveira
dc.creatorRonaldo Peres Costa
dc.creatorSilvana Maria Elói Santos
dc.creatorMatheus de Souza Gomes
dc.creatorLaurence Rodrigues do Amaral
dc.creatorAndréa Teixeira-carvalho
dc.date.accessioned2023-06-14T20:24:14Z
dc.date.accessioned2025-09-08T23:03:09Z
dc.date.available2023-06-14T20:24:14Z
dc.date.issued2016-01-25
dc.format.mimetypepdf
dc.identifier.doi10.1371/journal.pntd.0004302
dc.identifier.issn19352735
dc.identifier.urihttps://hdl.handle.net/1843/54940
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofPLOS Neglected Tropical Diseases
dc.rightsAcesso Aberto
dc.subjectDoença de Chagas
dc.subjectMacaca fascicularis
dc.subjectGranzimas
dc.subject.otherDoença de Chagas
dc.subject.otherMacaca fascicularis
dc.subject.otherGranzimas
dc.titlePhenotypic features of circulating leukocytes from non-human primates naturally infected with trypanosoma cruzi resemble the major immunological findings observed in human chagas disease
dc.typeArtigo de periódico
local.citation.epage16
local.citation.issue1
local.citation.spage1
local.citation.volume10
local.description.resumoCynomolgus 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. 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 infected with T. cruzi (CH) presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations 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 studiesapplied to development and testing of new drugs for Chagas disease.
local.publisher.countryBrasil
local.publisher.departmentMED - DEPARTAMENTO DE PROPEDÊUTICA COMPLEMENTAR
local.publisher.initialsUFMG
local.url.externahttps://doi:10.1371/journal.pntd.0004302

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