Header

UZH-Logo

Maintenance Infos

Airway microbiota determines innate cell inflammatory or tissue remodeling profiles in lung transplantation


Bernasconi, Eric; Pattaroni, Céline; Koutsokera, Angela; Pison, Christophe; Kessler, Romain; Benden, Christian; Soccal, Paola M; Magnan, Antoine; Aubert, John-David; Marsland, Benjamin J; Nicod, Laurent P; SysCLAD consortium (2016). Airway microbiota determines innate cell inflammatory or tissue remodeling profiles in lung transplantation. American Journal of Respiratory and Critical Care Medicine, 194(10):1252-1263.

Abstract

RATIONALE 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 dysfunction. Although advances in clinical practice have improved transplant success, the mechanisms by which the balance between inflammation and remodeling is maintained are largely unknown. OBJECTIVES To assess whether host-microbe interactions in the transplanted lung determine the immunologic tone of the airways, and consequently could impact graft survival. METHODS Microbiota DNA and host total RNA were isolated from 203 bronchoalveolar lavages obtained from 112 patients post-lung transplantation. Microbiota composition was determined using 16S ribosomal RNA analysis, and expression of a set of genes involved in prototypic macrophage functions was quantified using real-time quantitative polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS We show that the characteristics of the pulmonary microbiota aligned with distinct innate cell gene expression profiles. Although a nonpolarized activation was associated with bacterial communities consisting of a balance between proinflammatory (e.g., Staphylococcus and Pseudomonas) and low stimulatory (e.g., Prevotella and Streptococcus) bacteria, "inflammatory" and "remodeling" profiles were linked to bacterial dysbiosis. Mechanistic assays provided direct evidence that bacterial dysbiosis could lead to inflammatory or remodeling profiles in macrophages, whereas a balanced microbial community maintained homeostasis. CONCLUSIONS The crosstalk between bacterial communities and innate immune cells potentially determines the function of the transplanted lung offering novel pathways for intervention strategies.

Abstract

RATIONALE 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 dysfunction. Although advances in clinical practice have improved transplant success, the mechanisms by which the balance between inflammation and remodeling is maintained are largely unknown. OBJECTIVES To assess whether host-microbe interactions in the transplanted lung determine the immunologic tone of the airways, and consequently could impact graft survival. METHODS Microbiota DNA and host total RNA were isolated from 203 bronchoalveolar lavages obtained from 112 patients post-lung transplantation. Microbiota composition was determined using 16S ribosomal RNA analysis, and expression of a set of genes involved in prototypic macrophage functions was quantified using real-time quantitative polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS We show that the characteristics of the pulmonary microbiota aligned with distinct innate cell gene expression profiles. Although a nonpolarized activation was associated with bacterial communities consisting of a balance between proinflammatory (e.g., Staphylococcus and Pseudomonas) and low stimulatory (e.g., Prevotella and Streptococcus) bacteria, "inflammatory" and "remodeling" profiles were linked to bacterial dysbiosis. Mechanistic assays provided direct evidence that bacterial dysbiosis could lead to inflammatory or remodeling profiles in macrophages, whereas a balanced microbial community maintained homeostasis. CONCLUSIONS The crosstalk between bacterial communities and innate immune cells potentially determines the function of the transplanted lung offering novel pathways for intervention strategies.

Statistics

Citations

10 citations in Web of Science®
12 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Pneumology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:15 November 2016
Deposited On:20 Jan 2017 11:11
Last Modified:08 Dec 2017 22:12
Publisher:American Thoracic Society
ISSN:1073-449X
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1164/rccm.201512-2424OC
PubMed ID:27248293

Download

Full text not available from this repository.
View at publisher