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Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung

BACKGROUND: Homeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pat...

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Autores principales: Mouraux, Stéphane, Bernasconi, Eric, Pattaroni, Céline, Koutsokera, Angela, Aubert, John-David, Claustre, Johanna, Pison, Christophe, Royer, Pierre-Joseph, Magnan, Antoine, Kessler, Romain, Benden, Christian, Soccal, Paola M., Marsland, Benjamin J., Nicod, Laurent P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mosby 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5792246/
https://www.ncbi.nlm.nih.gov/pubmed/28729000
http://dx.doi.org/10.1016/j.jaci.2017.06.022
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author Mouraux, Stéphane
Bernasconi, Eric
Pattaroni, Céline
Koutsokera, Angela
Aubert, John-David
Claustre, Johanna
Pison, Christophe
Royer, Pierre-Joseph
Magnan, Antoine
Kessler, Romain
Benden, Christian
Soccal, Paola M.
Marsland, Benjamin J.
Nicod, Laurent P.
author_facet Mouraux, Stéphane
Bernasconi, Eric
Pattaroni, Céline
Koutsokera, Angela
Aubert, John-David
Claustre, Johanna
Pison, Christophe
Royer, Pierre-Joseph
Magnan, Antoine
Kessler, Romain
Benden, Christian
Soccal, Paola M.
Marsland, Benjamin J.
Nicod, Laurent P.
author_sort Mouraux, Stéphane
collection PubMed
description BACKGROUND: Homeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling. OBJECTIVE: This study assessed whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling posttransplantation. METHODS: Microbiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post lung transplantation. Expression of a set of 11 genes encoding either matrix components or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively) was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture. RESULTS: We identified 4 host gene expression profiles, among which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by proinflammatory bacteria (eg, Staphylococcus, Pseudomonas, and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (eg, Prevotella, Streptococcus, and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact host macrophage-fibroblast activation and matrix deposition. CONCLUSIONS: Host-microbes interplay potentially determines remodeling activities in the transplanted lung, highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome.
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spelling pubmed-57922462018-02-02 Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung Mouraux, Stéphane Bernasconi, Eric Pattaroni, Céline Koutsokera, Angela Aubert, John-David Claustre, Johanna Pison, Christophe Royer, Pierre-Joseph Magnan, Antoine Kessler, Romain Benden, Christian Soccal, Paola M. Marsland, Benjamin J. Nicod, Laurent P. J Allergy Clin Immunol Article BACKGROUND: Homeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling. OBJECTIVE: This study assessed whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling posttransplantation. METHODS: Microbiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post lung transplantation. Expression of a set of 11 genes encoding either matrix components or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively) was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture. RESULTS: We identified 4 host gene expression profiles, among which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by proinflammatory bacteria (eg, Staphylococcus, Pseudomonas, and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (eg, Prevotella, Streptococcus, and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact host macrophage-fibroblast activation and matrix deposition. CONCLUSIONS: Host-microbes interplay potentially determines remodeling activities in the transplanted lung, highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome. Mosby 2018-02 /pmc/articles/PMC5792246/ /pubmed/28729000 http://dx.doi.org/10.1016/j.jaci.2017.06.022 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Mouraux, Stéphane
Bernasconi, Eric
Pattaroni, Céline
Koutsokera, Angela
Aubert, John-David
Claustre, Johanna
Pison, Christophe
Royer, Pierre-Joseph
Magnan, Antoine
Kessler, Romain
Benden, Christian
Soccal, Paola M.
Marsland, Benjamin J.
Nicod, Laurent P.
Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung
title Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung
title_full Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung
title_fullStr Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung
title_full_unstemmed Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung
title_short Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung
title_sort airway microbiota signals anabolic and catabolic remodeling in the transplanted lung
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5792246/
https://www.ncbi.nlm.nih.gov/pubmed/28729000
http://dx.doi.org/10.1016/j.jaci.2017.06.022
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