Yadava, Koshika; Pattaroni, Céline; Sichelstiel, Anke K; Trompette, Aurélien; Gollwitzer, Eva S; Salami, Olawale; Von Garnier, Christophe; Nicod, Laurent P; Marsland, Benjamin J (2015). Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies. American journal of respiratory and critical care medicine, 193(9), pp. 975-987. American Lung Association 10.1164/rccm.201504-0779OC
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RATIONALE
Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease. Whether there is a causal relationship between these changes and disease progression remains unknown.
OBJECTIVE
To investigate the link between an altered microbiota and disease, we utilized a model of chronic lung inflammation in specific pathogen free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic).
METHODS
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.
MEASUREMENTS AND MAIN RESULTS
Similar to human disease, the composition of the pulmonary microbiota was altered in disease animals. We found that the microbiota richness and diversity were decreased in LPS/Elastase-treated mice, with an increased representation of the genera Pseudomonas, Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted of microbiota exhibited an improvement in lung function, reduction in airway inflammation, decrease in lymphoid neogenesis and auto-reactive antibody responses. The absence of microbial cues also markedly decreased the production of IL-17A, whilst 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.
CONCLUSIONS
Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology |
UniBE Contributor: |
von Garnier, Christophe |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1073-449X |
Publisher: |
American Lung Association |
Language: |
English |
Submitter: |
Rahel Holderegger |
Date Deposited: |
05 Apr 2016 16:30 |
Last Modified: |
02 Mar 2023 23:27 |
Publisher DOI: |
10.1164/rccm.201504-0779OC |
PubMed ID: |
26630356 |
BORIS DOI: |
10.7892/boris.78857 |
URI: |
https://boris.unibe.ch/id/eprint/78857 |
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