Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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
_version_ 1784677102096744448
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
work_keys_str_mv AT kotzeleighann targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT vanderspuygian targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT leonardbryan targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT pennnicholsonadam targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT musvosvimunyaradzi targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT mcandashirley targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT malherbestephanust targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT erasmusmzwandile targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT scribathomas targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT koegelenbergcoenraadfn targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT allwoodbrianw targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT walzlgerhard targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases
AT duplessisnelita targetedgeneexpressionprofilingofhumanmyeloidcellsfrombloodandlungcompartmentsofpatientswithtuberculosisandotherlungdiseases