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Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic, progressive, and growing worldwide health burden associated with mounting morbidity, mortality, and economic costs. Improvements in NTM-PD management are urgently needed, which requires a better understanding of fundamental immun...

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Autores principales: Ratnatunga, Champa N., Tungatt, Katie, Proietti, Carla, Halstrom, Sam, Holt, Michael R., Lutzky, Viviana P., Price, Patricia, Doolan, Denise L., Bell, Scott C., Field, Matt A., Kupz, Andreas, Thomson, Rachel M., Miles, John J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686449/
https://www.ncbi.nlm.nih.gov/pubmed/36439147
http://dx.doi.org/10.3389/fimmu.2022.1047781
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author Ratnatunga, Champa N.
Tungatt, Katie
Proietti, Carla
Halstrom, Sam
Holt, Michael R.
Lutzky, Viviana P.
Price, Patricia
Doolan, Denise L.
Bell, Scott C.
Field, Matt A.
Kupz, Andreas
Thomson, Rachel M.
Miles, John J.
author_facet Ratnatunga, Champa N.
Tungatt, Katie
Proietti, Carla
Halstrom, Sam
Holt, Michael R.
Lutzky, Viviana P.
Price, Patricia
Doolan, Denise L.
Bell, Scott C.
Field, Matt A.
Kupz, Andreas
Thomson, Rachel M.
Miles, John J.
author_sort Ratnatunga, Champa N.
collection PubMed
description Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic, progressive, and growing worldwide health burden associated with mounting morbidity, mortality, and economic costs. Improvements in NTM-PD management are urgently needed, which requires a better understanding of fundamental immunopathology. Here, we examine temporal dynamics of the immune compartment during NTM-PD caused by Mycobacterium avium complex (MAC) and Mycobactereoides abscessus complex (MABS). We show that active MAC infection is characterized by elevated T cell immunoglobulin and mucin-domain containing-3 expression across multiple T cell subsets. In contrast, active MABS infection was characterized by increased expression of cytotoxic T-lymphocyte-associated protein 4. Patients who failed therapy closely mirrored the healthy individual immune phenotype, with circulating immune network appearing to ‘ignore’ infection in the lung. Interestingly, immune biosignatures were identified that could inform disease stage and infecting species with high accuracy. Additionally, programmed cell death protein 1 blockade rescued antigen-specific IFN-γ secretion in all disease stages except persistent infection, suggesting the potential to redeploy checkpoint blockade inhibitors for NTM-PD. Collectively, our results provide new insight into species-specific ‘immune chatter’ occurring during NTM-PD and provide new targets, processes and pathways for diagnostics, prognostics, and treatments needed for this emerging and difficult to treat disease.
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spelling pubmed-96864492022-11-25 Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease Ratnatunga, Champa N. Tungatt, Katie Proietti, Carla Halstrom, Sam Holt, Michael R. Lutzky, Viviana P. Price, Patricia Doolan, Denise L. Bell, Scott C. Field, Matt A. Kupz, Andreas Thomson, Rachel M. Miles, John J. Front Immunol Immunology Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic, progressive, and growing worldwide health burden associated with mounting morbidity, mortality, and economic costs. Improvements in NTM-PD management are urgently needed, which requires a better understanding of fundamental immunopathology. Here, we examine temporal dynamics of the immune compartment during NTM-PD caused by Mycobacterium avium complex (MAC) and Mycobactereoides abscessus complex (MABS). We show that active MAC infection is characterized by elevated T cell immunoglobulin and mucin-domain containing-3 expression across multiple T cell subsets. In contrast, active MABS infection was characterized by increased expression of cytotoxic T-lymphocyte-associated protein 4. Patients who failed therapy closely mirrored the healthy individual immune phenotype, with circulating immune network appearing to ‘ignore’ infection in the lung. Interestingly, immune biosignatures were identified that could inform disease stage and infecting species with high accuracy. Additionally, programmed cell death protein 1 blockade rescued antigen-specific IFN-γ secretion in all disease stages except persistent infection, suggesting the potential to redeploy checkpoint blockade inhibitors for NTM-PD. Collectively, our results provide new insight into species-specific ‘immune chatter’ occurring during NTM-PD and provide new targets, processes and pathways for diagnostics, prognostics, and treatments needed for this emerging and difficult to treat disease. Frontiers Media S.A. 2022-11-10 /pmc/articles/PMC9686449/ /pubmed/36439147 http://dx.doi.org/10.3389/fimmu.2022.1047781 Text en Copyright © 2022 Ratnatunga, Tungatt, Proietti, Halstrom, Holt, Lutzky, Price, Doolan, Bell, Field, Kupz, Thomson and Miles 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
Ratnatunga, Champa N.
Tungatt, Katie
Proietti, Carla
Halstrom, Sam
Holt, Michael R.
Lutzky, Viviana P.
Price, Patricia
Doolan, Denise L.
Bell, Scott C.
Field, Matt A.
Kupz, Andreas
Thomson, Rachel M.
Miles, John J.
Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease
title Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease
title_full Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease
title_fullStr Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease
title_full_unstemmed Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease
title_short Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease
title_sort characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686449/
https://www.ncbi.nlm.nih.gov/pubmed/36439147
http://dx.doi.org/10.3389/fimmu.2022.1047781
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