title: Airway Microbiota Determines Innate Cell Inflammatory or Tissue Remodeling Profiles in Lung Transplantation.
abstract: 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.
  
  
  
  To assess whether host-microbe interactions in the transplanted lung determine the immunologic tone of the airways, and consequently could impact graft survival.
  
  
  
  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.
  
  
  
  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.
  
  
  
  The crosstalk between bacterial communities and innate immune cells potentially determines the function of the transplanted lung offering novel pathways for intervention strategies.
authors.affiliation: 1 Service de Pneumologie, Centre Hospitalier Universitaire Vaudois and Swiss Transplant Cohort Study, Lausanne, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Bernasconi
authors.affiliation: 1 Service de Pneumologie, Centre Hospitalier Universitaire Vaudois and Swiss Transplant Cohort Study, Lausanne, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Pattaroni
authors.affiliation: 1 Service de Pneumologie, Centre Hospitalier Universitaire Vaudois and Swiss Transplant Cohort Study, Lausanne, Switzerland.
authors.forename: Angela
authors.initials: A
authors.lastname: Koutsokera
authors.affiliation: 2 Clinique Universitaire de Pneumologie, Centre Hospitalier Universitaire (CHU), Grenoble, France.|3 Université Grenoble Alpes, Grenoble, France.|4 Inserm1055, Saint Martin d'Hères, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pison
authors.affiliation: 5 Service de Pneumologie, Nouvel Hôpital Civil, CHU, Strasbourg, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Kessler
authors.affiliation: 6 Division of Pulmonary Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Benden
authors.affiliation: 7 Division of Pulmonary Medicine, Geneva University Hospitals, Geneva, Switzerland; and.
authors.forename: Paola M
authors.initials: PM
authors.lastname: Soccal
authors.affiliation: 8 L'institut du thorax, Service de Pneumologie, CHU, Nantes, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Magnan
authors.affiliation: 1 Service de Pneumologie, Centre Hospitalier Universitaire Vaudois and Swiss Transplant Cohort Study, Lausanne, Switzerland.
authors.forename: John-David
authors.initials: JD
authors.lastname: Aubert
authors.affiliation: 1 Service de Pneumologie, Centre Hospitalier Universitaire Vaudois and Swiss Transplant Cohort Study, Lausanne, Switzerland.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Marsland
authors.affiliation: 1 Service de Pneumologie, Centre Hospitalier Universitaire Vaudois and Swiss Transplant Cohort Study, Lausanne, Switzerland.
authors.forename: Laurent P
authors.initials: LP
authors.lastname: Nicod
mesh_terms: D000328:Adult; D056151:Airway Remodeling / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D005260:Female; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000382:microbiology / Q000503:physiopathology*; D016040:Lung Transplantation; D008297:Male; D064307:Microbiota / Q000502:physiology*; D008875:Middle Aged; D012137:Respiratory System / Q000382:microbiology*
keywords: airway remodeling; macrophages; microbiome