Cargando…
T-cell deficiency and hyperinflammatory monocyte responses associate with Mycobacterium avium complex lung disease
Immunological mechanisms of susceptibility to nontuberculous mycobacterial (NTM) disease are poorly understood. To understand NTM pathogenesis, we evaluated innate and antigen-specific adaptive immune responses to Mycobacterium avium complex (MAC) in asymptomatic individuals with a previous history...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574438/ https://www.ncbi.nlm.nih.gov/pubmed/36263044 http://dx.doi.org/10.3389/fimmu.2022.1016038 |
_version_ | 1784811106128101376 |
---|---|
author | Lindestam Arlehamn, Cecilia S. Benson, Basilin Kuan, Rebecca Dill-McFarland, Kimberly A. Peterson, Glenna J. Paul, Sinu Nguyen, Felicia K. Gilman, Robert H. Saito, Mayuko Taplitz, Randy Arentz, Matthew Goss, Christopher H. Aitken, Moira L. Horne, David J. Shah, Javeed A. Sette, Alessandro Hawn, Thomas R. |
author_facet | Lindestam Arlehamn, Cecilia S. Benson, Basilin Kuan, Rebecca Dill-McFarland, Kimberly A. Peterson, Glenna J. Paul, Sinu Nguyen, Felicia K. Gilman, Robert H. Saito, Mayuko Taplitz, Randy Arentz, Matthew Goss, Christopher H. Aitken, Moira L. Horne, David J. Shah, Javeed A. Sette, Alessandro Hawn, Thomas R. |
author_sort | Lindestam Arlehamn, Cecilia S. |
collection | PubMed |
description | Immunological mechanisms of susceptibility to nontuberculous mycobacterial (NTM) disease are poorly understood. To understand NTM pathogenesis, we evaluated innate and antigen-specific adaptive immune responses to Mycobacterium avium complex (MAC) in asymptomatic individuals with a previous history of MAC lung disease (MACDZ). We hypothesized that Mav-specific immune responses are associated with susceptibility to MAC lung disease. We measured MAC-, NTM-, or MAC/Mtb-specific T-cell responses by cytokine production, expression of surface markers, and analysis of global gene expression in 27 MACDZ individuals and 32 healthy controls. We also analyzed global gene expression in Mycobacterium avium-infected and uninfected peripheral blood monocytes from 17 MACDZ and 17 healthy controls. We were unable to detect increased T-cell responses against MAC-specific reagents in MACDZ compared to controls, while the responses to non-mycobacteria derived antigens were preserved. MACDZ individuals had a lower frequency of Th1 and Th1* T-cell populations. In addition, MACDZ subjects had lower transcriptional responses in PBMCs stimulated with a mycobacterial peptide pool (MTB300). By contrast, global gene expression analysis demonstrated upregulation of proinflammatory pathways in uninfected and M. avium-infected monocytes, i.e. a hyperinflammatory in vitro response, derived from MACDZ subjects compared to controls. Together, these data suggest a novel immunologic defect which underlies MAC pathogenesis and includes concurrent innate and adaptive dysregulation which persists years after completion of treatment. |
format | Online Article Text |
id | pubmed-9574438 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95744382022-10-18 T-cell deficiency and hyperinflammatory monocyte responses associate with Mycobacterium avium complex lung disease Lindestam Arlehamn, Cecilia S. Benson, Basilin Kuan, Rebecca Dill-McFarland, Kimberly A. Peterson, Glenna J. Paul, Sinu Nguyen, Felicia K. Gilman, Robert H. Saito, Mayuko Taplitz, Randy Arentz, Matthew Goss, Christopher H. Aitken, Moira L. Horne, David J. Shah, Javeed A. Sette, Alessandro Hawn, Thomas R. Front Immunol Immunology Immunological mechanisms of susceptibility to nontuberculous mycobacterial (NTM) disease are poorly understood. To understand NTM pathogenesis, we evaluated innate and antigen-specific adaptive immune responses to Mycobacterium avium complex (MAC) in asymptomatic individuals with a previous history of MAC lung disease (MACDZ). We hypothesized that Mav-specific immune responses are associated with susceptibility to MAC lung disease. We measured MAC-, NTM-, or MAC/Mtb-specific T-cell responses by cytokine production, expression of surface markers, and analysis of global gene expression in 27 MACDZ individuals and 32 healthy controls. We also analyzed global gene expression in Mycobacterium avium-infected and uninfected peripheral blood monocytes from 17 MACDZ and 17 healthy controls. We were unable to detect increased T-cell responses against MAC-specific reagents in MACDZ compared to controls, while the responses to non-mycobacteria derived antigens were preserved. MACDZ individuals had a lower frequency of Th1 and Th1* T-cell populations. In addition, MACDZ subjects had lower transcriptional responses in PBMCs stimulated with a mycobacterial peptide pool (MTB300). By contrast, global gene expression analysis demonstrated upregulation of proinflammatory pathways in uninfected and M. avium-infected monocytes, i.e. a hyperinflammatory in vitro response, derived from MACDZ subjects compared to controls. Together, these data suggest a novel immunologic defect which underlies MAC pathogenesis and includes concurrent innate and adaptive dysregulation which persists years after completion of treatment. Frontiers Media S.A. 2022-10-03 /pmc/articles/PMC9574438/ /pubmed/36263044 http://dx.doi.org/10.3389/fimmu.2022.1016038 Text en Copyright © 2022 Lindestam Arlehamn, Benson, Kuan, Dill-McFarland, Peterson, Paul, Nguyen, Gilman, Saito, Taplitz, Arentz, Goss, Aitken, Horne, Shah, Sette and Hawn 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 Lindestam Arlehamn, Cecilia S. Benson, Basilin Kuan, Rebecca Dill-McFarland, Kimberly A. Peterson, Glenna J. Paul, Sinu Nguyen, Felicia K. Gilman, Robert H. Saito, Mayuko Taplitz, Randy Arentz, Matthew Goss, Christopher H. Aitken, Moira L. Horne, David J. Shah, Javeed A. Sette, Alessandro Hawn, Thomas R. T-cell deficiency and hyperinflammatory monocyte responses associate with Mycobacterium avium complex lung disease |
title | T-cell deficiency and hyperinflammatory monocyte responses associate with Mycobacterium avium complex lung disease |
title_full | T-cell deficiency and hyperinflammatory monocyte responses associate with Mycobacterium avium complex lung disease |
title_fullStr | T-cell deficiency and hyperinflammatory monocyte responses associate with Mycobacterium avium complex lung disease |
title_full_unstemmed | T-cell deficiency and hyperinflammatory monocyte responses associate with Mycobacterium avium complex lung disease |
title_short | T-cell deficiency and hyperinflammatory monocyte responses associate with Mycobacterium avium complex lung disease |
title_sort | t-cell deficiency and hyperinflammatory monocyte responses associate with mycobacterium avium complex lung disease |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574438/ https://www.ncbi.nlm.nih.gov/pubmed/36263044 http://dx.doi.org/10.3389/fimmu.2022.1016038 |
work_keys_str_mv | AT lindestamarlehamncecilias tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT bensonbasilin tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT kuanrebecca tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT dillmcfarlandkimberlya tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT petersonglennaj tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT paulsinu tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT nguyenfeliciak tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT gilmanroberth tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT saitomayuko tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT taplitzrandy tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT arentzmatthew tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT gosschristopherh tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT aitkenmoiral tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT hornedavidj tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT shahjaveeda tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT settealessandro tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease AT hawnthomasr tcelldeficiencyandhyperinflammatorymonocyteresponsesassociatewithmycobacteriumaviumcomplexlungdisease |