Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies

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

Preview

Text rccm.pdf - Accepted Version Available under License Publisher holds Copyright. Download (3MB) | Preview

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.

Interest & Impact

Downloads

1003 since deposited on 05 Apr 2016
154 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item