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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 (...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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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. |
format | Online Article Text |
id | pubmed-8493473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
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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