Distinct CD4−CD8− (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease

CD4−CD8− (double-negative, DN) T cells are critical orchestrators of the cytokine network associated with the pathogenic inflammatory response in one of the deadliest cardiomyopathies known, Chagas heart disease, which is caused by Trypanosoma cruzi infection. Here, studying the distribution, activa...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Livia Silva Araújo Passos, Carolina Cattoni Koh, Luísa Mourão Dias Magalhães, Maria do Carmo Pereira Nunes, Kenneth John Gollob, Walderez Ornelas Dutra
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Trypanosoma cruzi pathology immunoregulation Chagas disease cardiomyopathy memory response Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/d31da241a2fd433a8cf475850fd0577f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d31da241a2fd433a8cf475850fd0577f
record_format	dspace
spelling	oai:doaj.org-article:d31da241a2fd433a8cf475850fd0577f2021-11-11T12:26:28ZDistinct CD4−CD8− (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease1664-322410.3389/fimmu.2021.761795https://doaj.org/article/d31da241a2fd433a8cf475850fd0577f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.761795/fullhttps://doaj.org/toc/1664-3224CD4−CD8− (double-negative, DN) T cells are critical orchestrators of the cytokine network associated with the pathogenic inflammatory response in one of the deadliest cardiomyopathies known, Chagas heart disease, which is caused by Trypanosoma cruzi infection. Here, studying the distribution, activation status, and cytokine expression of memory DN T-cell subpopulations in Chagas disease patients without cardiac involvement (indeterminate form—IND) or with Chagas cardiomyopathy (CARD), we report that while IND patients displayed a higher frequency of central memory, CARD had a high frequency of effector memory DN T cells. In addition, central memory DN T cells from IND displayed a balanced cytokine profile, characterized by the concomitant expression of IFN-γ and IL-10, which was not observed in effector memory DN T cells from CARD. Supporting potential clinical relevance, we found that the frequency of central memory DN T cells was associated with indicators of better ventricular function, while the frequency of effector memory DN T cells was not. Importantly, decreasing CD1d-mediated activation of DN T cells led to an increase in IL-10 expression by effector memory DN T cells from CARD, restoring a balanced profile similar to that observed in the protective central memory DN T cells. Targeting the activation of effector memory DN T cells may emerge as a strategy to control inflammation in Chagas cardiomyopathy and potentially in other inflammatory diseases where these cells play a key role.Livia Silva Araújo PassosLivia Silva Araújo PassosCarolina Cattoni KohLuísa Mourão Dias MagalhãesLuísa Mourão Dias MagalhãesMaria do Carmo Pereira NunesKenneth John GollobKenneth John GollobWalderez Ornelas DutraWalderez Ornelas DutraWalderez Ornelas DutraFrontiers Media S.A.articleTrypanosoma cruzipathologyimmunoregulationChagas diseasecardiomyopathymemory responseImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Trypanosoma cruzi pathology immunoregulation Chagas disease cardiomyopathy memory response Immunologic diseases. Allergy RC581-607
spellingShingle	Trypanosoma cruzi pathology immunoregulation Chagas disease cardiomyopathy memory response Immunologic diseases. Allergy RC581-607 Livia Silva Araújo Passos Livia Silva Araújo Passos Carolina Cattoni Koh Luísa Mourão Dias Magalhães Luísa Mourão Dias Magalhães Maria do Carmo Pereira Nunes Kenneth John Gollob Kenneth John Gollob Walderez Ornelas Dutra Walderez Ornelas Dutra Walderez Ornelas Dutra Distinct CD4−CD8− (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
description	CD4−CD8− (double-negative, DN) T cells are critical orchestrators of the cytokine network associated with the pathogenic inflammatory response in one of the deadliest cardiomyopathies known, Chagas heart disease, which is caused by Trypanosoma cruzi infection. Here, studying the distribution, activation status, and cytokine expression of memory DN T-cell subpopulations in Chagas disease patients without cardiac involvement (indeterminate form—IND) or with Chagas cardiomyopathy (CARD), we report that while IND patients displayed a higher frequency of central memory, CARD had a high frequency of effector memory DN T cells. In addition, central memory DN T cells from IND displayed a balanced cytokine profile, characterized by the concomitant expression of IFN-γ and IL-10, which was not observed in effector memory DN T cells from CARD. Supporting potential clinical relevance, we found that the frequency of central memory DN T cells was associated with indicators of better ventricular function, while the frequency of effector memory DN T cells was not. Importantly, decreasing CD1d-mediated activation of DN T cells led to an increase in IL-10 expression by effector memory DN T cells from CARD, restoring a balanced profile similar to that observed in the protective central memory DN T cells. Targeting the activation of effector memory DN T cells may emerge as a strategy to control inflammation in Chagas cardiomyopathy and potentially in other inflammatory diseases where these cells play a key role.
format	article
author	Livia Silva Araújo Passos Livia Silva Araújo Passos Carolina Cattoni Koh Luísa Mourão Dias Magalhães Luísa Mourão Dias Magalhães Maria do Carmo Pereira Nunes Kenneth John Gollob Kenneth John Gollob Walderez Ornelas Dutra Walderez Ornelas Dutra Walderez Ornelas Dutra
author_facet	Livia Silva Araújo Passos Livia Silva Araújo Passos Carolina Cattoni Koh Luísa Mourão Dias Magalhães Luísa Mourão Dias Magalhães Maria do Carmo Pereira Nunes Kenneth John Gollob Kenneth John Gollob Walderez Ornelas Dutra Walderez Ornelas Dutra Walderez Ornelas Dutra
author_sort	Livia Silva Araújo Passos
title	Distinct CD4−CD8− (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
title_short	Distinct CD4−CD8− (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
title_full	Distinct CD4−CD8− (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
title_fullStr	Distinct CD4−CD8− (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
title_full_unstemmed	Distinct CD4−CD8− (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease
title_sort	distinct cd4−cd8− (double-negative) memory t-cell subpopulations are associated with indeterminate and cardiac clinical forms of chagas disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d31da241a2fd433a8cf475850fd0577f
work_keys_str_mv	AT liviasilvaaraujopassos distinctcd4cd8doublenegativememorytcellsubpopulationsareassociatedwithindeterminateandcardiacclinicalformsofchagasdisease AT liviasilvaaraujopassos distinctcd4cd8doublenegativememorytcellsubpopulationsareassociatedwithindeterminateandcardiacclinicalformsofchagasdisease AT carolinacattonikoh distinctcd4cd8doublenegativememorytcellsubpopulationsareassociatedwithindeterminateandcardiacclinicalformsofchagasdisease AT luisamouraodiasmagalhaes distinctcd4cd8doublenegativememorytcellsubpopulationsareassociatedwithindeterminateandcardiacclinicalformsofchagasdisease AT luisamouraodiasmagalhaes distinctcd4cd8doublenegativememorytcellsubpopulationsareassociatedwithindeterminateandcardiacclinicalformsofchagasdisease AT mariadocarmopereiranunes distinctcd4cd8doublenegativememorytcellsubpopulationsareassociatedwithindeterminateandcardiacclinicalformsofchagasdisease AT kennethjohngollob distinctcd4cd8doublenegativememorytcellsubpopulationsareassociatedwithindeterminateandcardiacclinicalformsofchagasdisease AT kennethjohngollob distinctcd4cd8doublenegativememorytcellsubpopulationsareassociatedwithindeterminateandcardiacclinicalformsofchagasdisease AT walderezornelasdutra distinctcd4cd8doublenegativememorytcellsubpopulationsareassociatedwithindeterminateandcardiacclinicalformsofchagasdisease AT walderezornelasdutra distinctcd4cd8doublenegativememorytcellsubpopulationsareassociatedwithindeterminateandcardiacclinicalformsofchagasdisease AT walderezornelasdutra distinctcd4cd8doublenegativememorytcellsubpopulationsareassociatedwithindeterminateandcardiacclinicalformsofchagasdisease
_version_	1718439078995689472

Distinct CD4−CD8− (Double-Negative) Memory T-Cell Subpopulations Are Associated With Indeterminate and Cardiac Clinical Forms of Chagas Disease

Ejemplares similares