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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
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