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Phenotypic profiling of CD8(+) T cells during Plasmodium vivax blood-stage infection

BACKGROUND: For a long time, the role of CD8(+) T cells in blood-stage malaria was not considered important because erythrocytes do not express major histocompatibility complex (MHC) class I proteins. While recent evidences suggest that CD8(+) T cells may play an important role during the erythrocyt...

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Autores principales: Hojo-Souza, Natália Satchiko, Pereira, Dhelio Batista, Passos, Lívia Silva Araújo, Gazzinelli-Guimarães, Pedro Henrique, Cardoso, Mariana Santos, Tada, Mauro Shugiro, Zanini, Graziela Maria, Bartholomeu, Daniella Castanheira, Fujiwara, Ricardo Toshio, Bueno, Lilian Lacerda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329216/
https://www.ncbi.nlm.nih.gov/pubmed/25636730
http://dx.doi.org/10.1186/s12879-015-0762-x
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author Hojo-Souza, Natália Satchiko
Pereira, Dhelio Batista
Passos, Lívia Silva Araújo
Gazzinelli-Guimarães, Pedro Henrique
Cardoso, Mariana Santos
Tada, Mauro Shugiro
Zanini, Graziela Maria
Bartholomeu, Daniella Castanheira
Fujiwara, Ricardo Toshio
Bueno, Lilian Lacerda
author_facet Hojo-Souza, Natália Satchiko
Pereira, Dhelio Batista
Passos, Lívia Silva Araújo
Gazzinelli-Guimarães, Pedro Henrique
Cardoso, Mariana Santos
Tada, Mauro Shugiro
Zanini, Graziela Maria
Bartholomeu, Daniella Castanheira
Fujiwara, Ricardo Toshio
Bueno, Lilian Lacerda
author_sort Hojo-Souza, Natália Satchiko
collection PubMed
description BACKGROUND: For a long time, the role of CD8(+) T cells in blood-stage malaria was not considered important because erythrocytes do not express major histocompatibility complex (MHC) class I proteins. While recent evidences suggest that CD8(+) T cells may play an important role during the erythrocytic phase of infection by eliminating parasites, CD8(+) T cells might also contribute to modulate the host response through production of regulatory cytokines. Thus, the role of CD8(+) T cells during blood-stage malaria is unclear. Here, we report the phenotypic profiling of CD8(+) T cells subsets from patients with uncomplicated symptomatic P. vivax malaria. METHODS: Blood samples were collected from 20 Plasmodium vivax-infected individuals and 12 healthy individuals. Immunophenotyping was conducted by flow cytometry. Plasma levels of IFN-γ, TNF-α and IL-10 were determined by ELISA/CBA. Unpaired t-test or Mann–Whitney test was used depending on the data distribution. RESULTS: P. vivax-infected subjects had lower percentages and absolute numbers of CD8(+)CD45RA(+) and CD8(+)CD45RO(+) T cells when compared to uninfected individuals (p ≤ 0.0002). A significantly lower absolute number of circulating CD8(+)CD45(+)CCR7(+) cells (p = 0.002) was observed in P. vivax-infected individuals indicating that infection reduces the number of central memory T cells. Cytokine expression was significantly reduced in the naïve T cells from infected individuals compared with negative controls, as shown by lower numbers of IFN-γ(+) (p = 0.001), TNF-α(+) (p < 0.0001) and IL-10(+) (p < 0.0001) CD8(+) T cells. Despite the reduction in the number of CD8(+) memory T cells producing IFN-γ (p < 0.0001), P. vivax-infected individuals demonstrated a significant increase in memory CD8(+)TNF-α(+) (p = 0.016) and CD8(+)IL-10(+) (p = 0.004) cells. Positive correlations were observed between absolute numbers of CD8(+)IL-10(+) and numbers of CD8(+)IFN-γ(+) (p < 0.001) and CD8(+)TNF-α(+) T cells (p ≤ 0.0001). Finally, an increase in the plasma levels of TNF-α (p = 0.017) and IL-10 (p = 0.006) and a decrease in the IFN-γ plasma level (p <0.0001) were observed in the P. vivax-infected individuals. CONCLUSIONS: P. vivax infection reduces the numbers of different subsets of CD8(+) T cells, particularly the memory cells, during blood-stage of infection and enhances the number of CD8(+) memory T cells expressing IL-10, which positively correlates with the number of cells expressing TNF-α and IFN-γ. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0762-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-43292162015-02-16 Phenotypic profiling of CD8(+) T cells during Plasmodium vivax blood-stage infection Hojo-Souza, Natália Satchiko Pereira, Dhelio Batista Passos, Lívia Silva Araújo Gazzinelli-Guimarães, Pedro Henrique Cardoso, Mariana Santos Tada, Mauro Shugiro Zanini, Graziela Maria Bartholomeu, Daniella Castanheira Fujiwara, Ricardo Toshio Bueno, Lilian Lacerda BMC Infect Dis Research Article BACKGROUND: For a long time, the role of CD8(+) T cells in blood-stage malaria was not considered important because erythrocytes do not express major histocompatibility complex (MHC) class I proteins. While recent evidences suggest that CD8(+) T cells may play an important role during the erythrocytic phase of infection by eliminating parasites, CD8(+) T cells might also contribute to modulate the host response through production of regulatory cytokines. Thus, the role of CD8(+) T cells during blood-stage malaria is unclear. Here, we report the phenotypic profiling of CD8(+) T cells subsets from patients with uncomplicated symptomatic P. vivax malaria. METHODS: Blood samples were collected from 20 Plasmodium vivax-infected individuals and 12 healthy individuals. Immunophenotyping was conducted by flow cytometry. Plasma levels of IFN-γ, TNF-α and IL-10 were determined by ELISA/CBA. Unpaired t-test or Mann–Whitney test was used depending on the data distribution. RESULTS: P. vivax-infected subjects had lower percentages and absolute numbers of CD8(+)CD45RA(+) and CD8(+)CD45RO(+) T cells when compared to uninfected individuals (p ≤ 0.0002). A significantly lower absolute number of circulating CD8(+)CD45(+)CCR7(+) cells (p = 0.002) was observed in P. vivax-infected individuals indicating that infection reduces the number of central memory T cells. Cytokine expression was significantly reduced in the naïve T cells from infected individuals compared with negative controls, as shown by lower numbers of IFN-γ(+) (p = 0.001), TNF-α(+) (p < 0.0001) and IL-10(+) (p < 0.0001) CD8(+) T cells. Despite the reduction in the number of CD8(+) memory T cells producing IFN-γ (p < 0.0001), P. vivax-infected individuals demonstrated a significant increase in memory CD8(+)TNF-α(+) (p = 0.016) and CD8(+)IL-10(+) (p = 0.004) cells. Positive correlations were observed between absolute numbers of CD8(+)IL-10(+) and numbers of CD8(+)IFN-γ(+) (p < 0.001) and CD8(+)TNF-α(+) T cells (p ≤ 0.0001). Finally, an increase in the plasma levels of TNF-α (p = 0.017) and IL-10 (p = 0.006) and a decrease in the IFN-γ plasma level (p <0.0001) were observed in the P. vivax-infected individuals. CONCLUSIONS: P. vivax infection reduces the numbers of different subsets of CD8(+) T cells, particularly the memory cells, during blood-stage of infection and enhances the number of CD8(+) memory T cells expressing IL-10, which positively correlates with the number of cells expressing TNF-α and IFN-γ. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0762-x) contains supplementary material, which is available to authorized users. BioMed Central 2015-01-31 /pmc/articles/PMC4329216/ /pubmed/25636730 http://dx.doi.org/10.1186/s12879-015-0762-x Text en © Hojo-Souza et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Hojo-Souza, Natália Satchiko
Pereira, Dhelio Batista
Passos, Lívia Silva Araújo
Gazzinelli-Guimarães, Pedro Henrique
Cardoso, Mariana Santos
Tada, Mauro Shugiro
Zanini, Graziela Maria
Bartholomeu, Daniella Castanheira
Fujiwara, Ricardo Toshio
Bueno, Lilian Lacerda
Phenotypic profiling of CD8(+) T cells during Plasmodium vivax blood-stage infection
title Phenotypic profiling of CD8(+) T cells during Plasmodium vivax blood-stage infection
title_full Phenotypic profiling of CD8(+) T cells during Plasmodium vivax blood-stage infection
title_fullStr Phenotypic profiling of CD8(+) T cells during Plasmodium vivax blood-stage infection
title_full_unstemmed Phenotypic profiling of CD8(+) T cells during Plasmodium vivax blood-stage infection
title_short Phenotypic profiling of CD8(+) T cells during Plasmodium vivax blood-stage infection
title_sort phenotypic profiling of cd8(+) t cells during plasmodium vivax blood-stage infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329216/
https://www.ncbi.nlm.nih.gov/pubmed/25636730
http://dx.doi.org/10.1186/s12879-015-0762-x
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