Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung

Stéphane Mouraux, Eric Bernasconi, Céline Pattaroni, Angela Koutsokera, John David Aubert, Johanna Claustre, Christophe Pison, Pierre Joseph Royer, Antoine Magnan, Romain Kessler, Christian Benden, Paola M. Soccal, Benjamin J. Marsland, Laurent P. Nicod

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

LanguageEnglish
Pages718–729.e7
Number of pages19
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number2
DOIs
Publication statusPublished - Feb 2018
Externally publishedYes

Keywords

  • Airway remodeling
  • Fibroblasts
  • Macrophages
  • Matrix
  • Microbiota

Cite this

Mouraux, S., Bernasconi, E., Pattaroni, C., Koutsokera, A., Aubert, J. D., Claustre, J., ... Nicod, L. P. (2018). Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung. Journal of Allergy and Clinical Immunology, 141(2), 718–729.e7. https://doi.org/10.1016/j.jaci.2017.06.022
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. In: Journal of Allergy and Clinical Immunology. 2018 ; Vol. 141, No. 2. pp. 718–729.e7.
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abstract = "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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Mouraux, S, Bernasconi, E, Pattaroni, C, Koutsokera, A, Aubert, JD, Claustre, J, Pison, C, Royer, PJ, Magnan, A, Kessler, R, Benden, C, Soccal, PM, Marsland, BJ & Nicod, LP 2018, 'Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung' Journal of Allergy and Clinical Immunology, vol. 141, no. 2, pp. 718–729.e7. https://doi.org/10.1016/j.jaci.2017.06.022

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.

In: Journal of Allergy and Clinical Immunology, Vol. 141, No. 2, 02.2018, p. 718–729.e7.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung

AU - Mouraux, Stéphane

AU - Bernasconi, Eric

AU - Pattaroni, Céline

AU - Koutsokera, Angela

AU - Aubert, John David

AU - Claustre, Johanna

AU - Pison, Christophe

AU - Royer, Pierre Joseph

AU - Magnan, Antoine

AU - Kessler, Romain

AU - Benden, Christian

AU - Soccal, Paola M.

AU - Marsland, Benjamin J.

AU - Nicod, Laurent P.

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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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