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CD4(+) T cells apoptosis in Plasmodium vivax infection is mediated by activation of both intrinsic and extrinsic pathways

BACKGROUND: Reduction in the number of circulating blood lymphocytes (lymphocytopaenia) has been reported during clinical episodes of malaria and is normalized after treatment with anti-malaria drugs. While this phenomenon is well established in malaria infection, the underlying mechanisms are still...

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Autores principales: Hojo-Souza, Natália S, Pereira, Dhelio B, Mendes, Tiago AO, Passos, Lívia SA, Gazzinelli-Guimarães, Ana Clara, Gazzinelli-Guimarães, Pedro H, Tada, Mauro S, Zanini, Graziela M, Bartholomeu, Daniella C, Fujiwara, Ricardo T, Bueno, Lilian L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326293/
https://www.ncbi.nlm.nih.gov/pubmed/25559491
http://dx.doi.org/10.1186/1475-2875-14-5
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author Hojo-Souza, Natália S
Pereira, Dhelio B
Mendes, Tiago AO
Passos, Lívia SA
Gazzinelli-Guimarães, Ana Clara
Gazzinelli-Guimarães, Pedro H
Tada, Mauro S
Zanini, Graziela M
Bartholomeu, Daniella C
Fujiwara, Ricardo T
Bueno, Lilian L
author_facet Hojo-Souza, Natália S
Pereira, Dhelio B
Mendes, Tiago AO
Passos, Lívia SA
Gazzinelli-Guimarães, Ana Clara
Gazzinelli-Guimarães, Pedro H
Tada, Mauro S
Zanini, Graziela M
Bartholomeu, Daniella C
Fujiwara, Ricardo T
Bueno, Lilian L
author_sort Hojo-Souza, Natália S
collection PubMed
description BACKGROUND: Reduction in the number of circulating blood lymphocytes (lymphocytopaenia) has been reported during clinical episodes of malaria and is normalized after treatment with anti-malaria drugs. While this phenomenon is well established in malaria infection, the underlying mechanisms are still not fully elucidated. In the present study, the occurrence of apoptosis and its pathways in CD4(+) T cells was investigated in naturally Plasmodium vivax-infected individuals from a Brazilian endemic area (Porto Velho – RO). METHODS: Blood samples were collected from P. vivax-infected individuals and healthy donors. The apoptosis was characterized by cell staining with Annexin V/FITC and propidium iodide and the apoptosis-associated gene expression profile was carried out using RT(2) Profiler PCR Array–Human Apoptosis. The plasma TNF level was determined by ELISA. The unpaired t-test or Mann–Whitney test was applied according to the data distribution. RESULTS: Plasmodium vivax-infected individuals present low number of leukocytes and lymphocytes with a higher percentage of CD4(+) T cells in early and/or late apoptosis. Increased gene expression was observed for TNFRSF1B and Bid, associated with a reduction of Bcl-2, in individuals with P. vivax malaria. Furthermore, these individuals showed increased plasma levels of TNF compared to malaria-naive donors. CONCLUSIONS: The results of the present study suggest that P. vivax infection induces apoptosis of CD4(+) T cells mediated by two types of signaling: by activation of the TNFR1 death receptor (extrinsic pathway), which is amplified by Bid, and by decreased expression of the anti-apoptotic protein Bcl-2 (intrinsic pathway). The T lymphocytes apoptosis could reflect a strategy of immune evasion triggered by the parasite, enabling their persistence but also limiting the occurrence of immunopathology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1475-2875-14-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-43262932015-02-14 CD4(+) T cells apoptosis in Plasmodium vivax infection is mediated by activation of both intrinsic and extrinsic pathways Hojo-Souza, Natália S Pereira, Dhelio B Mendes, Tiago AO Passos, Lívia SA Gazzinelli-Guimarães, Ana Clara Gazzinelli-Guimarães, Pedro H Tada, Mauro S Zanini, Graziela M Bartholomeu, Daniella C Fujiwara, Ricardo T Bueno, Lilian L Malar J Research BACKGROUND: Reduction in the number of circulating blood lymphocytes (lymphocytopaenia) has been reported during clinical episodes of malaria and is normalized after treatment with anti-malaria drugs. While this phenomenon is well established in malaria infection, the underlying mechanisms are still not fully elucidated. In the present study, the occurrence of apoptosis and its pathways in CD4(+) T cells was investigated in naturally Plasmodium vivax-infected individuals from a Brazilian endemic area (Porto Velho – RO). METHODS: Blood samples were collected from P. vivax-infected individuals and healthy donors. The apoptosis was characterized by cell staining with Annexin V/FITC and propidium iodide and the apoptosis-associated gene expression profile was carried out using RT(2) Profiler PCR Array–Human Apoptosis. The plasma TNF level was determined by ELISA. The unpaired t-test or Mann–Whitney test was applied according to the data distribution. RESULTS: Plasmodium vivax-infected individuals present low number of leukocytes and lymphocytes with a higher percentage of CD4(+) T cells in early and/or late apoptosis. Increased gene expression was observed for TNFRSF1B and Bid, associated with a reduction of Bcl-2, in individuals with P. vivax malaria. Furthermore, these individuals showed increased plasma levels of TNF compared to malaria-naive donors. CONCLUSIONS: The results of the present study suggest that P. vivax infection induces apoptosis of CD4(+) T cells mediated by two types of signaling: by activation of the TNFR1 death receptor (extrinsic pathway), which is amplified by Bid, and by decreased expression of the anti-apoptotic protein Bcl-2 (intrinsic pathway). The T lymphocytes apoptosis could reflect a strategy of immune evasion triggered by the parasite, enabling their persistence but also limiting the occurrence of immunopathology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1475-2875-14-5) contains supplementary material, which is available to authorized users. BioMed Central 2015-01-05 /pmc/articles/PMC4326293/ /pubmed/25559491 http://dx.doi.org/10.1186/1475-2875-14-5 Text en © Hojo-Souza et al.; licensee BioMed Central. 2015 This article is published under license to BioMed Central Ltd. 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
Hojo-Souza, Natália S
Pereira, Dhelio B
Mendes, Tiago AO
Passos, Lívia SA
Gazzinelli-Guimarães, Ana Clara
Gazzinelli-Guimarães, Pedro H
Tada, Mauro S
Zanini, Graziela M
Bartholomeu, Daniella C
Fujiwara, Ricardo T
Bueno, Lilian L
CD4(+) T cells apoptosis in Plasmodium vivax infection is mediated by activation of both intrinsic and extrinsic pathways
title CD4(+) T cells apoptosis in Plasmodium vivax infection is mediated by activation of both intrinsic and extrinsic pathways
title_full CD4(+) T cells apoptosis in Plasmodium vivax infection is mediated by activation of both intrinsic and extrinsic pathways
title_fullStr CD4(+) T cells apoptosis in Plasmodium vivax infection is mediated by activation of both intrinsic and extrinsic pathways
title_full_unstemmed CD4(+) T cells apoptosis in Plasmodium vivax infection is mediated by activation of both intrinsic and extrinsic pathways
title_short CD4(+) T cells apoptosis in Plasmodium vivax infection is mediated by activation of both intrinsic and extrinsic pathways
title_sort cd4(+) t cells apoptosis in plasmodium vivax infection is mediated by activation of both intrinsic and extrinsic pathways
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326293/
https://www.ncbi.nlm.nih.gov/pubmed/25559491
http://dx.doi.org/10.1186/1475-2875-14-5
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