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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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