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Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases
Myeloid-derived suppressor cells (MDSC) have been identified in the peripheral blood and granulomas of patients with active TB disease, but their phenotype-, function-, and immunosuppressive mechanism- spectrum remains unclear. Importantly, the frequency and signaling pathways of MDSC at the site of...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959218/ https://www.ncbi.nlm.nih.gov/pubmed/35356003 http://dx.doi.org/10.3389/fimmu.2022.839747 |
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author | Kotze, Leigh Ann van der Spuy, Gian Leonard, Bryan Penn-Nicholson, Adam Musvosvi, Munyaradzi McAnda, Shirley Malherbe, Stephanus T. Erasmus, Mzwandile Scriba, Thomas Koegelenberg, Coenraad F. N. Allwood, Brian W. Walzl, Gerhard du Plessis, Nelita |
author_facet | Kotze, Leigh Ann van der Spuy, Gian Leonard, Bryan Penn-Nicholson, Adam Musvosvi, Munyaradzi McAnda, Shirley Malherbe, Stephanus T. Erasmus, Mzwandile Scriba, Thomas Koegelenberg, Coenraad F. N. Allwood, Brian W. Walzl, Gerhard du Plessis, Nelita |
author_sort | Kotze, Leigh Ann |
collection | PubMed |
description | Myeloid-derived suppressor cells (MDSC) have been identified in the peripheral blood and granulomas of patients with active TB disease, but their phenotype-, function-, and immunosuppressive mechanism- spectrum remains unclear. Importantly, the frequency and signaling pathways of MDSC at the site of disease is unknown with no indication how this compares to MDSC identified in peripheral blood or to those of related myeloid counterparts such as alveolar macrophages and monocytes. Most phenotypic and functional markers have been described in oncological studies but have not yet been validated in TB. Using a panel of 43 genes selected from pathways previously shown to contribute to tumor-derived MDSC, we set out to evaluate if the expression of these additional functional markers and properties may also be relevant to TB-derived MDSC. Differential expression was investigated between MDSC, alveolar macrophages and monocytes enriched from bronchoalveolar lavage fluid and peripheral blood of patients with active TB, patients with other lung diseases (OLD). Results demonstrated that anatomical compartments may drive compartment-specific immunological responses and subsequent MDSC immunosuppressive functions, demonstrated by the observation that MDSC and/or monocytes from PB alone can discriminate, via hierarchical clustering, between patients with active TB disease and OLD. Our data show that the gene expression patterns of MDSC in peripheral blood and bronchoalveolar lavage fluid do not cluster according to disease states (TB vs OLD). This suggests that MDSC from TB patients may display similar gene expression profiles to those found for MDSC in cancer, but this needs to be validated in a larger cohort. These are important observations for TB research and may provide direction for future studies aimed at repurposing and validating cancer immunotherapies for use in TB. |
format | Online Article Text |
id | pubmed-8959218 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89592182022-03-29 Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases Kotze, Leigh Ann van der Spuy, Gian Leonard, Bryan Penn-Nicholson, Adam Musvosvi, Munyaradzi McAnda, Shirley Malherbe, Stephanus T. Erasmus, Mzwandile Scriba, Thomas Koegelenberg, Coenraad F. N. Allwood, Brian W. Walzl, Gerhard du Plessis, Nelita Front Immunol Immunology Myeloid-derived suppressor cells (MDSC) have been identified in the peripheral blood and granulomas of patients with active TB disease, but their phenotype-, function-, and immunosuppressive mechanism- spectrum remains unclear. Importantly, the frequency and signaling pathways of MDSC at the site of disease is unknown with no indication how this compares to MDSC identified in peripheral blood or to those of related myeloid counterparts such as alveolar macrophages and monocytes. Most phenotypic and functional markers have been described in oncological studies but have not yet been validated in TB. Using a panel of 43 genes selected from pathways previously shown to contribute to tumor-derived MDSC, we set out to evaluate if the expression of these additional functional markers and properties may also be relevant to TB-derived MDSC. Differential expression was investigated between MDSC, alveolar macrophages and monocytes enriched from bronchoalveolar lavage fluid and peripheral blood of patients with active TB, patients with other lung diseases (OLD). Results demonstrated that anatomical compartments may drive compartment-specific immunological responses and subsequent MDSC immunosuppressive functions, demonstrated by the observation that MDSC and/or monocytes from PB alone can discriminate, via hierarchical clustering, between patients with active TB disease and OLD. Our data show that the gene expression patterns of MDSC in peripheral blood and bronchoalveolar lavage fluid do not cluster according to disease states (TB vs OLD). This suggests that MDSC from TB patients may display similar gene expression profiles to those found for MDSC in cancer, but this needs to be validated in a larger cohort. These are important observations for TB research and may provide direction for future studies aimed at repurposing and validating cancer immunotherapies for use in TB. Frontiers Media S.A. 2022-03-08 /pmc/articles/PMC8959218/ /pubmed/35356003 http://dx.doi.org/10.3389/fimmu.2022.839747 Text en Copyright © 2022 Kotze, van der Spuy, Leonard, Penn-Nicholson, Musvosvi, McAnda, Malherbe, Erasmus, Scriba, Koegelenberg, Allwood, Walzl and du Plessis https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Kotze, Leigh Ann van der Spuy, Gian Leonard, Bryan Penn-Nicholson, Adam Musvosvi, Munyaradzi McAnda, Shirley Malherbe, Stephanus T. Erasmus, Mzwandile Scriba, Thomas Koegelenberg, Coenraad F. N. Allwood, Brian W. Walzl, Gerhard du Plessis, Nelita Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases |
title | Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases |
title_full | Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases |
title_fullStr | Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases |
title_full_unstemmed | Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases |
title_short | Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases |
title_sort | targeted gene expression profiling of human myeloid cells from blood and lung compartments of patients with tuberculosis and other lung diseases |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959218/ https://www.ncbi.nlm.nih.gov/pubmed/35356003 http://dx.doi.org/10.3389/fimmu.2022.839747 |
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