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Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis

Conventional anti-tuberculosis (TB) therapies comprise lengthy antibiotic treatment regimens, exacerbated by multi-drug resistant and extensively drug resistant mycobacterial strains. We assessed the ability of all-trans retinoic acid (ATRA), as repurposed compound serving as host-directed therapy (...

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Autores principales: Leukes, Vinzeigh N., Dorhoi, Anca, Malherbe, Stephanus T., Maasdorp, Elizna, Khoury, Justine, McAnda, Shirley, Walzl, Gerhard, du Plessis, Nelita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493473/
https://www.ncbi.nlm.nih.gov/pubmed/33865151
http://dx.doi.org/10.1016/j.cellimm.2021.104359
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author Leukes, Vinzeigh N.
Dorhoi, Anca
Malherbe, Stephanus T.
Maasdorp, Elizna
Khoury, Justine
McAnda, Shirley
Walzl, Gerhard
du Plessis, Nelita
author_facet Leukes, Vinzeigh N.
Dorhoi, Anca
Malherbe, Stephanus T.
Maasdorp, Elizna
Khoury, Justine
McAnda, Shirley
Walzl, Gerhard
du Plessis, Nelita
author_sort Leukes, Vinzeigh N.
collection PubMed
description Conventional anti-tuberculosis (TB) therapies comprise lengthy antibiotic treatment regimens, exacerbated by multi-drug resistant and extensively drug resistant mycobacterial strains. We assessed the ability of all-trans retinoic acid (ATRA), as repurposed compound serving as host-directed therapy (HDT), to counteract the suppressive effects of myeloid-derived suppressor cells (MDSCs) obtained from active TB cases (untreated or during week one of treatment) on T-cell responsiveness. We show for the first time that MDSCs suppress non-specific T-cell activation and production of interleukin (IL)-2, IL-4, IL-13 and GM-CSF via contact-dependent mechanisms. ATRA treatment decreases MDSC frequency, but fails to mature MDSCs to non-suppressive, terminally differentiated myeloid cells and does not restore T-cell function or cytokine production in the presence of MDSCs. The impact of ATRA treatment on improved immunity, using the concentration tested here, is likely to be minimal, but further identification and development of MDSC-targeting TB host-directed therapies are warranted.
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spelling pubmed-84934732021-10-06 Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis Leukes, Vinzeigh N. Dorhoi, Anca Malherbe, Stephanus T. Maasdorp, Elizna Khoury, Justine McAnda, Shirley Walzl, Gerhard du Plessis, Nelita Cell Immunol Article Conventional anti-tuberculosis (TB) therapies comprise lengthy antibiotic treatment regimens, exacerbated by multi-drug resistant and extensively drug resistant mycobacterial strains. We assessed the ability of all-trans retinoic acid (ATRA), as repurposed compound serving as host-directed therapy (HDT), to counteract the suppressive effects of myeloid-derived suppressor cells (MDSCs) obtained from active TB cases (untreated or during week one of treatment) on T-cell responsiveness. We show for the first time that MDSCs suppress non-specific T-cell activation and production of interleukin (IL)-2, IL-4, IL-13 and GM-CSF via contact-dependent mechanisms. ATRA treatment decreases MDSC frequency, but fails to mature MDSCs to non-suppressive, terminally differentiated myeloid cells and does not restore T-cell function or cytokine production in the presence of MDSCs. The impact of ATRA treatment on improved immunity, using the concentration tested here, is likely to be minimal, but further identification and development of MDSC-targeting TB host-directed therapies are warranted. 2021-04-08 2021-06 /pmc/articles/PMC8493473/ /pubmed/33865151 http://dx.doi.org/10.1016/j.cellimm.2021.104359 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Leukes, Vinzeigh N.
Dorhoi, Anca
Malherbe, Stephanus T.
Maasdorp, Elizna
Khoury, Justine
McAnda, Shirley
Walzl, Gerhard
du Plessis, Nelita
Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis
title Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis
title_full Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis
title_fullStr Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis
title_full_unstemmed Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis
title_short Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis
title_sort targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493473/
https://www.ncbi.nlm.nih.gov/pubmed/33865151
http://dx.doi.org/10.1016/j.cellimm.2021.104359
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