Afficher la couverture 'Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung | Mouraux, Stéphane' en grand format
/5

0 avis

Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung

Archive ouverte

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.

Edité par CCSD ; Elsevier -

International audience. 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.

Suggestions

Du même auteur

Airway Microbiota Determines Innate Cell Inflammatory or Tissue Remodeling Profiles in Lung Transplantation

Archive ouverte | Bernasconi, Eric | CCSD

International audience. In lung transplant recipients, long-term graft survival relies on the control of inflammation and tissue remodeling to maintain graft functionality and avoid chronic lung allograft dysfunctio...

Development of a multivariate prediction model for early-onset bronchiolitis obliterans syndrome and restrictive allograft syndrome in lung transplantation

Archive ouverte | Koutsokera, Angela | CCSD

International audience. Background: Chronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after l...

Chronic Lung Allograft Dysfunction: A Systematic Review of Mechanisms

Archive ouverte | Royer, Pierre-Joseph | CCSD

International audience. Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans sy...

Chargement des enrichissements...