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Increase of CD4(+)CD25(high)FoxP3(+) cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis
BACKGROUND: 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 Tre...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321116/ https://www.ncbi.nlm.nih.gov/pubmed/34324509 http://dx.doi.org/10.1371/journal.pntd.0009605 |
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author | Stringari, Lorenzzo Lyrio Covre, Luciana Polaco da Silva, Flávia Dias Coelho de Oliveira, Vivian Leite Campana, Maria Carolina Hadad, David Jamil Palaci, Moisés Salgame, Padmini Dietze, Reynaldo Gomes, Daniel Cláudio de Oliveira Ribeiro-Rodrigues, Rodrigo |
author_facet | Stringari, Lorenzzo Lyrio Covre, Luciana Polaco da Silva, Flávia Dias Coelho de Oliveira, Vivian Leite Campana, Maria Carolina Hadad, David Jamil Palaci, Moisés Salgame, Padmini Dietze, Reynaldo Gomes, Daniel Cláudio de Oliveira Ribeiro-Rodrigues, Rodrigo |
author_sort | Stringari, Lorenzzo Lyrio |
collection | PubMed |
description | BACKGROUND: 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. METHODS: 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). RESULTS: The frequency of CD4(+)CD25(high)FoxP3(+) 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(+)CD25(high)FoxP3(+) is associated with an impairment of Th-1 responses and a diminished in vitro microbicidal activity of LTBI and TB groups. CONCLUSIONS: Tregs restrict host anti-mycobacterial immunity during active disease and latent infection and thereby may contribute to both disease progression and pathogen persistence. |
format | Online Article Text |
id | pubmed-8321116 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-83211162021-07-31 Increase of CD4(+)CD25(high)FoxP3(+) cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis Stringari, Lorenzzo Lyrio Covre, Luciana Polaco da Silva, Flávia Dias Coelho de Oliveira, Vivian Leite Campana, Maria Carolina Hadad, David Jamil Palaci, Moisés Salgame, Padmini Dietze, Reynaldo Gomes, Daniel Cláudio de Oliveira Ribeiro-Rodrigues, Rodrigo PLoS Negl Trop Dis Research Article BACKGROUND: 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. METHODS: 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). RESULTS: The frequency of CD4(+)CD25(high)FoxP3(+) 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(+)CD25(high)FoxP3(+) is associated with an impairment of Th-1 responses and a diminished in vitro microbicidal activity of LTBI and TB groups. CONCLUSIONS: Tregs restrict host anti-mycobacterial immunity during active disease and latent infection and thereby may contribute to both disease progression and pathogen persistence. Public Library of Science 2021-07-29 /pmc/articles/PMC8321116/ /pubmed/34324509 http://dx.doi.org/10.1371/journal.pntd.0009605 Text en © 2021 Stringari et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Stringari, Lorenzzo Lyrio Covre, Luciana Polaco da Silva, Flávia Dias Coelho de Oliveira, Vivian Leite Campana, Maria Carolina Hadad, David Jamil Palaci, Moisés Salgame, Padmini Dietze, Reynaldo Gomes, Daniel Cláudio de Oliveira Ribeiro-Rodrigues, Rodrigo Increase of CD4(+)CD25(high)FoxP3(+) cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis |
title | Increase of CD4(+)CD25(high)FoxP3(+) cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis |
title_full | Increase of CD4(+)CD25(high)FoxP3(+) cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis |
title_fullStr | Increase of CD4(+)CD25(high)FoxP3(+) cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis |
title_full_unstemmed | Increase of CD4(+)CD25(high)FoxP3(+) cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis |
title_short | Increase of CD4(+)CD25(high)FoxP3(+) cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis |
title_sort | increase of cd4(+)cd25(high)foxp3(+) cells impairs in vitro human microbicidal activity against mycobacterium tuberculosis during latent and acute pulmonary tuberculosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321116/ https://www.ncbi.nlm.nih.gov/pubmed/34324509 http://dx.doi.org/10.1371/journal.pntd.0009605 |
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