title: Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies.
abstract: Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease (COPD). Whether there is a causal relationship between these changes and disease progression remains unknown.
  
  
  
  To investigate the link between an altered microbiota and disease, we used a murine model of chronic lung inflammation that is characterized by key pathological features found in COPD and compared responses in specific pathogen-free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic).
  
  
  
  Mice were challenged with LPS/elastase intranasally over 4 weeks, resulting in a chronically inflamed and damaged lung. The ensuing cellular infiltration, histological damage, and decline in lung function were quantified.
  
  
  
  Similar to human disease, the composition of the pulmonary microbiota was altered in diseased animals. We found that the microbiota richness and diversity were decreased in LPS/elastase-treated mice, with an increased representation of the genera Pseudomonas and Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted, or devoid, of microbiota exhibited an improvement in lung function, reduced inflammation, and lymphoid neogenesis. The absence of microbial cues markedly decreased the production of IL-17A, whereas intranasal transfer of fluid enriched with the pulmonary microbiota isolated from diseased mice enhanced IL-17A production in the lungs of antibiotic-treated or axenic recipients. Finally, in mice harboring a microbiota, neutralizing IL-17A dampened inflammation and restored lung function.
  
  
  
  Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.
authors.affiliation: 1 Service de Pneumologie, Faculté de Biologie et de Médecine, Centre Hospitalier Universitaire Vaudoise-Université Lausanne Lausanne, Switzerland.|2 Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Koshika
authors.initials: K
authors.lastname: Yadava
authors.affiliation: 1 Service de Pneumologie, Faculté de Biologie et de Médecine, Centre Hospitalier Universitaire Vaudoise-Université Lausanne Lausanne, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Pattaroni
authors.affiliation: 1 Service de Pneumologie, Faculté de Biologie et de Médecine, Centre Hospitalier Universitaire Vaudoise-Université Lausanne Lausanne, Switzerland.
authors.forename: Anke K
authors.initials: AK
authors.lastname: Sichelstiel
authors.affiliation: 1 Service de Pneumologie, Faculté de Biologie et de Médecine, Centre Hospitalier Universitaire Vaudoise-Université Lausanne Lausanne, Switzerland.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Trompette
authors.affiliation: 1 Service de Pneumologie, Faculté de Biologie et de Médecine, Centre Hospitalier Universitaire Vaudoise-Université Lausanne Lausanne, Switzerland.
authors.forename: Eva S
authors.initials: ES
authors.lastname: Gollwitzer
authors.affiliation: 1 Service de Pneumologie, Faculté de Biologie et de Médecine, Centre Hospitalier Universitaire Vaudoise-Université Lausanne Lausanne, Switzerland.
authors.forename: Olawale
authors.initials: O
authors.lastname: Salami
authors.affiliation: 3 Department of Respiratory Medicine, Inselspital, Bern University Hospital, Bern, Switzerland; and.|4 Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: von Garnier
authors.affiliation: 1 Service de Pneumologie, Faculté de Biologie et de Médecine, Centre Hospitalier Universitaire Vaudoise-Université Lausanne Lausanne, Switzerland.
authors.forename: Laurent P
authors.initials: LP
authors.lastname: Nicod
authors.affiliation: 1 Service de Pneumologie, Faculté de Biologie et de Médecine, Centre Hospitalier Universitaire Vaudoise-Université Lausanne Lausanne, Switzerland.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Marsland
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D020381:Interleukin-17 / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D064307:Microbiota; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000276:immunology* / Q000503:physiopathology*
chemical_list: D001323:Autoantibodies; D020381:Interleukin-17
keywords: microbiome; COPD; autoimmunity; IL-17