Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease.
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 accom...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0004302 https://doaj.org/article/2f39a4f99ec84abb97acc06341a4bbf0 |
id |
ftdoajarticles:oai:doaj.org/article:2f39a4f99ec84abb97acc06341a4bbf0 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:2f39a4f99ec84abb97acc06341a4bbf0 2023-05-15T15:14:22+02:00 Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease. Renato Sathler-Avelar Danielle Marquete Vitelli-Avelar Armanda Moreira Mattoso-Barbosa Marcelo Perdigão-de-Oliveira Ronaldo Peres Costa Silvana Maria Elói-Santos Matheus de Souza Gomes Laurence Rodrigues do Amaral Andréa Teixeira-Carvalho Olindo Assis Martins-Filho Edward J Dick Gene B Hubbard Jane F VandeBerg John L VandeBerg 2016-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004302 https://doaj.org/article/2f39a4f99ec84abb97acc06341a4bbf0 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4726540?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004302 https://doaj.org/article/2f39a4f99ec84abb97acc06341a4bbf0 PLoS Neglected Tropical Diseases, Vol 10, Iss 1, p e0004302 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004302 2022-12-31T12:03:17Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 1 e0004302 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Renato Sathler-Avelar Danielle Marquete Vitelli-Avelar Armanda Moreira Mattoso-Barbosa Marcelo Perdigão-de-Oliveira Ronaldo Peres Costa Silvana Maria Elói-Santos Matheus de Souza Gomes Laurence Rodrigues do Amaral Andréa Teixeira-Carvalho Olindo Assis Martins-Filho Edward J Dick Gene B Hubbard Jane F VandeBerg John L VandeBerg Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Renato Sathler-Avelar Danielle Marquete Vitelli-Avelar Armanda Moreira Mattoso-Barbosa Marcelo Perdigão-de-Oliveira Ronaldo Peres Costa Silvana Maria Elói-Santos Matheus de Souza Gomes Laurence Rodrigues do Amaral Andréa Teixeira-Carvalho Olindo Assis Martins-Filho Edward J Dick Gene B Hubbard Jane F VandeBerg John L VandeBerg |
author_facet |
Renato Sathler-Avelar Danielle Marquete Vitelli-Avelar Armanda Moreira Mattoso-Barbosa Marcelo Perdigão-de-Oliveira Ronaldo Peres Costa Silvana Maria Elói-Santos Matheus de Souza Gomes Laurence Rodrigues do Amaral Andréa Teixeira-Carvalho Olindo Assis Martins-Filho Edward J Dick Gene B Hubbard Jane F VandeBerg John L VandeBerg |
author_sort |
Renato Sathler-Avelar |
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. |
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. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0004302 https://doaj.org/article/2f39a4f99ec84abb97acc06341a4bbf0 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 1, p e0004302 (2016) |
op_relation |
http://europepmc.org/articles/PMC4726540?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004302 https://doaj.org/article/2f39a4f99ec84abb97acc06341a4bbf0 |
op_doi |
https://doi.org/10.1371/journal.pntd.0004302 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
10 |
container_issue |
1 |
container_start_page |
e0004302 |
_version_ |
1766344834037055488 |