Eric Bernasconi1, Céline Pattaroni1, Angela Koutsokera1, Christophe Pison2,3,4, Romain Kessler5, Christian Benden6, Paola M Soccal7, Antoine Magnan8, John-David Aubert1, Benjamin J Marsland1, Laurent P Nicod1. 1. 1 Service de Pneumologie, Centre Hospitalier Universitaire Vaudois and Swiss Transplant Cohort Study, Lausanne, Switzerland. 2. 2 Clinique Universitaire de Pneumologie, Centre Hospitalier Universitaire (CHU), Grenoble, France. 3. 3 Université Grenoble Alpes, Grenoble, France. 4. 4 Inserm1055, Saint Martin d'Hères, France. 5. 5 Service de Pneumologie, Nouvel Hôpital Civil, CHU, Strasbourg, France. 6. 6 Division of Pulmonary Medicine, University Hospital Zurich, Zurich, Switzerland. 7. 7 Division of Pulmonary Medicine, Geneva University Hospitals, Geneva, Switzerland; and. 8. 8 L'institut du thorax, Service de Pneumologie, CHU, Nantes, France.
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.
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.
Authors: Qiang Wu; Benjamin Turturice; Sarah Wagner; Yue Huang; Pawan Kumar Gupta; Cody Schott; Ahmed Metwally; Ravi Ranjan; David Perkins; Maria-Luisa Alegre; Patricia Finn; G R Scott Budinger; Rebecca Shilling; Ankit Bharat Journal: Am J Respir Cell Mol Biol Date: 2019-01 Impact factor: 6.914
Authors: Nirmal S Sharma; Keith M Wille; S Athira; Degui Zhi; Kenneth P Hough; Enrique Diaz-Guzman; Kui Zhang; Ranjit Kumar; Sunad Rangarajan; Peter Eipers; Yong Wang; Ritesh K Srivastava; Jose Vicente Rodriguez Dager; Mohammad Athar; Casey Morrow; Charles W Hoopes; David D Chaplin; Victor J Thannickal; Jessy S Deshane Journal: J Heart Lung Transplant Date: 2017-07-15 Impact factor: 10.247
Authors: Lynn D Haynes; Walker A Julliard; Joshua D Mezrich; Glen Leverson; Keith C Meyer; William J Burlingham Journal: Transplantation Date: 2018-07 Impact factor: 4.939
Authors: Kurtis F Budden; Shaan L Gellatly; David L A Wood; Matthew A Cooper; Mark Morrison; Philip Hugenholtz; Philip M Hansbro Journal: Nat Rev Microbiol Date: 2016-10-03 Impact factor: 60.633