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PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease
Tuberculosis (TB), due to Mycobacterium tuberculosis infection, is still the principal cause of death caused by a single infectious agent. The balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. Factors defining this variety are unclear an...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107479/ https://www.ncbi.nlm.nih.gov/pubmed/33981297 http://dx.doi.org/10.3389/fimmu.2021.594376 |
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author | Grassi, Germana Vanini, Valentina De Santis, Federica Romagnoli, Alessandra Aiello, Alessandra Casetti, Rita Cimini, Eleonora Bordoni, Veronica Notari, Stefania Cuzzi, Gilda Mosti, Silvia Gualano, Gina Palmieri, Fabrizio Fraziano, Maurizio Goletti, Delia Agrati, Chiara Sacchi, Alessandra |
author_facet | Grassi, Germana Vanini, Valentina De Santis, Federica Romagnoli, Alessandra Aiello, Alessandra Casetti, Rita Cimini, Eleonora Bordoni, Veronica Notari, Stefania Cuzzi, Gilda Mosti, Silvia Gualano, Gina Palmieri, Fabrizio Fraziano, Maurizio Goletti, Delia Agrati, Chiara Sacchi, Alessandra |
author_sort | Grassi, Germana |
collection | PubMed |
description | Tuberculosis (TB), due to Mycobacterium tuberculosis infection, is still the principal cause of death caused by a single infectious agent. The balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. Factors defining this variety are unclear and likely involve both mycobacterial and immunological components. Myeloid derived suppressor cells (MDSC) have been shown to be expanded during TB, but their role in human TB pathogenesis is not clear. We evaluated the frequency of circulating MDSC by flow-cytometry in 19 patients with active TB, 18 with latent TB infection (LTBI), and 12 healthy donors (HD) as control. Moreover, we investigated the capacity of MDSC to modulate the mycobactericidal activity of monocytes. The association between MDSC level and TB chest X-ray severity score was analyzed. We observed that, unlike active TB, polymorphonuclear (PMN)-MDSC are not expanded in LTBI patients, and, by performing a receiver operating characteristic (ROC) curve analysis, we found that PMN-MDSC frequency supported the discrimination between active disease and LTBI. Interestingly, we observed an association between PMN-MDSC levels and the severity of TB disease evaluated by chest X-ray. Specifically, PMN-MDSC frequency was higher in those classified with a low/mild severity score compared to those classified with a high severity score. Moreover, PMN-MDSC can impact mycobacterial growth by inducing ROS production in Bacillus Calmette et Guerin (BCG)-infected monocytes. This effect was lost when tested with M. tuberculosis (MTB), In conclusion, our data indicate that the elevated frequency of PMN-MDSC in IGRA-positive individuals is associated with active TB. Our findings also pointed out a beneficial role of PMN-MDSC during human active TB, most likely associated with the limitation of inflammation-induced tissue damage. |
format | Online Article Text |
id | pubmed-8107479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81074792021-05-11 PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease Grassi, Germana Vanini, Valentina De Santis, Federica Romagnoli, Alessandra Aiello, Alessandra Casetti, Rita Cimini, Eleonora Bordoni, Veronica Notari, Stefania Cuzzi, Gilda Mosti, Silvia Gualano, Gina Palmieri, Fabrizio Fraziano, Maurizio Goletti, Delia Agrati, Chiara Sacchi, Alessandra Front Immunol Immunology Tuberculosis (TB), due to Mycobacterium tuberculosis infection, is still the principal cause of death caused by a single infectious agent. The balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. Factors defining this variety are unclear and likely involve both mycobacterial and immunological components. Myeloid derived suppressor cells (MDSC) have been shown to be expanded during TB, but their role in human TB pathogenesis is not clear. We evaluated the frequency of circulating MDSC by flow-cytometry in 19 patients with active TB, 18 with latent TB infection (LTBI), and 12 healthy donors (HD) as control. Moreover, we investigated the capacity of MDSC to modulate the mycobactericidal activity of monocytes. The association between MDSC level and TB chest X-ray severity score was analyzed. We observed that, unlike active TB, polymorphonuclear (PMN)-MDSC are not expanded in LTBI patients, and, by performing a receiver operating characteristic (ROC) curve analysis, we found that PMN-MDSC frequency supported the discrimination between active disease and LTBI. Interestingly, we observed an association between PMN-MDSC levels and the severity of TB disease evaluated by chest X-ray. Specifically, PMN-MDSC frequency was higher in those classified with a low/mild severity score compared to those classified with a high severity score. Moreover, PMN-MDSC can impact mycobacterial growth by inducing ROS production in Bacillus Calmette et Guerin (BCG)-infected monocytes. This effect was lost when tested with M. tuberculosis (MTB), In conclusion, our data indicate that the elevated frequency of PMN-MDSC in IGRA-positive individuals is associated with active TB. Our findings also pointed out a beneficial role of PMN-MDSC during human active TB, most likely associated with the limitation of inflammation-induced tissue damage. Frontiers Media S.A. 2021-04-26 /pmc/articles/PMC8107479/ /pubmed/33981297 http://dx.doi.org/10.3389/fimmu.2021.594376 Text en Copyright © 2021 Grassi, Vanini, De Santis, Romagnoli, Aiello, Casetti, Cimini, Bordoni, Notari, Cuzzi, Mosti, Gualano, Palmieri, Fraziano, Goletti, Agrati and Sacchi 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 Grassi, Germana Vanini, Valentina De Santis, Federica Romagnoli, Alessandra Aiello, Alessandra Casetti, Rita Cimini, Eleonora Bordoni, Veronica Notari, Stefania Cuzzi, Gilda Mosti, Silvia Gualano, Gina Palmieri, Fabrizio Fraziano, Maurizio Goletti, Delia Agrati, Chiara Sacchi, Alessandra PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease |
title | PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease |
title_full | PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease |
title_fullStr | PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease |
title_full_unstemmed | PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease |
title_short | PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease |
title_sort | pmn-mdsc frequency discriminates active versus latent tuberculosis and could play a role in counteracting the immune-mediated lung damage in active disease |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107479/ https://www.ncbi.nlm.nih.gov/pubmed/33981297 http://dx.doi.org/10.3389/fimmu.2021.594376 |
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