Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung

Publication date: Available online 18 July 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): 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
BackgroundHomeostatic 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 (CLAD), an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling.ObjectiveTo assess whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling post-transplantation.MethodsMicrobiota 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.ResultsWe identified four host gene expression profiles, amongst 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 pro-inflammatory bacteria (e.g. Staphylococcus, Pseudomonas and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (e.g. Prevotella, Streptococcus and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact upon host macrophage-fibroblast activation and matrix deposition.ConclusionHost-microbes interplay potentially determines remodeling activities in the transplanted lung highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome.

Teaser

The rate of matrix deposition varies with the microbial composition in the transplanted lung, potentially impacting upon graft survival.


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