Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis.

<h4>Background</h4>Regulatory T cells (Tregs) play a critical role during Mycobacterium tuberculosis (Mtb) infection, modulating host responses while neutralizing excessive inflammation. However, their impact on regulating host protective immunity is not completely understood. Here, we d...

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Autores principales:	Lorenzzo Lyrio Stringari, Luciana Polaco Covre, Flávia Dias Coelho da Silva, Vivian Leite de Oliveira, Maria Carolina Campana, David Jamil Hadad, Moisés Palaci, Padmini Salgame, Reynaldo Dietze, Daniel Cláudio de Oliveira Gomes, Rodrigo Ribeiro-Rodrigues
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/e834ab677b0548a2913ae039f2c55a56
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spelling	oai:doaj.org-article:e834ab677b0548a2913ae039f2c55a562021-11-25T06:33:26ZIncrease of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis.1935-27271935-273510.1371/journal.pntd.0009605https://doaj.org/article/e834ab677b0548a2913ae039f2c55a562021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009605https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Regulatory T cells (Tregs) play a critical role during Mycobacterium tuberculosis (Mtb) infection, modulating host responses while neutralizing excessive inflammation. However, their impact on regulating host protective immunity is not completely understood. Here, we demonstrate that Treg cells abrogate the in vitro microbicidal activity against Mtb.<h4>Methods</h4>We evaluated the in vitro microbicidal activity of peripheral blood mononuclear cells (PBMCs) from patients with active tuberculosis (TB), individuals with latent tuberculosis infection (LTBI, TST+/IGRA+) and healthy control (HC, TST-/IGRA-) volunteers. PBMCs, depleted or not of CD4+CD25+ T-cells, were analyzed to determine frequency and influence on microbicidal activity during in vitro Mtb infection with four clinical isolates (S1, S5, R3, and R6) and one reference strain (H37Rv).<h4>Results</h4>The frequency of CD4+CD25highFoxP3+ cells were significantly higher in Mtb infected whole blood cultures from both TB patients and LTBI individuals when compared to HC. Data from CD4+CD25+ T-cells depletion demonstrate that increase of CD4+CD25highFoxP3+ is associated with an impairment of Th-1 responses and a diminished in vitro microbicidal activity of LTBI and TB groups.<h4>Conclusions</h4>Tregs restrict host anti-mycobacterial immunity during active disease and latent infection and thereby may contribute to both disease progression and pathogen persistence.Lorenzzo Lyrio StringariLuciana Polaco CovreFlávia Dias Coelho da SilvaVivian Leite de OliveiraMaria Carolina CampanaDavid Jamil HadadMoisés PalaciPadmini SalgameReynaldo DietzeDaniel Cláudio de Oliveira GomesRodrigo Ribeiro-RodriguesPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 7, p e0009605 (2021)
institution	DOAJ
collection	DOAJ
language	EN
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 Lorenzzo Lyrio Stringari Luciana Polaco Covre Flávia Dias Coelho da Silva Vivian Leite de Oliveira Maria Carolina Campana David Jamil Hadad Moisés Palaci Padmini Salgame Reynaldo Dietze Daniel Cláudio de Oliveira Gomes Rodrigo Ribeiro-Rodrigues Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis.
description	<h4>Background</h4>Regulatory T cells (Tregs) play a critical role during Mycobacterium tuberculosis (Mtb) infection, modulating host responses while neutralizing excessive inflammation. However, their impact on regulating host protective immunity is not completely understood. Here, we demonstrate that Treg cells abrogate the in vitro microbicidal activity against Mtb.<h4>Methods</h4>We evaluated the in vitro microbicidal activity of peripheral blood mononuclear cells (PBMCs) from patients with active tuberculosis (TB), individuals with latent tuberculosis infection (LTBI, TST+/IGRA+) and healthy control (HC, TST-/IGRA-) volunteers. PBMCs, depleted or not of CD4+CD25+ T-cells, were analyzed to determine frequency and influence on microbicidal activity during in vitro Mtb infection with four clinical isolates (S1, S5, R3, and R6) and one reference strain (H37Rv).<h4>Results</h4>The frequency of CD4+CD25highFoxP3+ cells were significantly higher in Mtb infected whole blood cultures from both TB patients and LTBI individuals when compared to HC. Data from CD4+CD25+ T-cells depletion demonstrate that increase of CD4+CD25highFoxP3+ is associated with an impairment of Th-1 responses and a diminished in vitro microbicidal activity of LTBI and TB groups.<h4>Conclusions</h4>Tregs restrict host anti-mycobacterial immunity during active disease and latent infection and thereby may contribute to both disease progression and pathogen persistence.
format	article
author	Lorenzzo Lyrio Stringari Luciana Polaco Covre Flávia Dias Coelho da Silva Vivian Leite de Oliveira Maria Carolina Campana David Jamil Hadad Moisés Palaci Padmini Salgame Reynaldo Dietze Daniel Cláudio de Oliveira Gomes Rodrigo Ribeiro-Rodrigues
author_facet	Lorenzzo Lyrio Stringari Luciana Polaco Covre Flávia Dias Coelho da Silva Vivian Leite de Oliveira Maria Carolina Campana David Jamil Hadad Moisés Palaci Padmini Salgame Reynaldo Dietze Daniel Cláudio de Oliveira Gomes Rodrigo Ribeiro-Rodrigues
author_sort	Lorenzzo Lyrio Stringari
title	Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis.
title_short	Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis.
title_full	Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis.
title_fullStr	Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis.
title_full_unstemmed	Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis.
title_sort	increase of cd4+cd25highfoxp3+ cells impairs in vitro human microbicidal activity against mycobacterium tuberculosis during latent and acute pulmonary tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e834ab677b0548a2913ae039f2c55a56
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Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis.

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