Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Sabelo Hadebe, Frank Kirstein, Kaat Fierens, Kong Chen, Rebecca A. Drummond, Simon Vautier, Sara Sajaniemi, Graeme Murray, David L. Williams, Pierre Redelinghuys, Todd A. Reinhart, Beth A.Fallert Junecko, Jay K. Kolls, Bart N. Lambrecht, Frank Brombacher, Gordon D. Brown

Research output: Contribution to journalArticle

26 Citations (Scopus)
5 Downloads (Pure)

Abstract

Asthma is a heterogeneous disease whose etiology is poorly understood but is likely to involve innate responses to inhaled microbial components that are found in allergens. The influence of these components on pulmonary inflammation has been largely studied in the context of individual agonists, despite knowledge that they can have synergistic effects when used in combination. Here we have explored the effects of LPS and β-glucan, two commonly-encountered microbial agonists, on the pathogenesis of allergic and non-allergic respiratory responses to house dust mite allergen. Notably, sensitization with these micro-bial components in combination acted synergistically to promote robust neutrophilic inflammation, which involved both Dectin-1 and TLR-4. This pulmonary neutrophilic inflammation was corticosteroid-refractory, resembling that found in patients with severe asthma. Thus our results provide key new insights into how microbial components influence the development of respiratory pathology.

Original languageEnglish
Article numbere0134219
Number of pages17
JournalPLoS ONE
Volume10
Issue number8
DOIs
Publication statusPublished - 11 Aug 2015
Externally publishedYes

    Fingerprint

Bibliographical note

Copyright: © 2015 Hadebe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright © and Moral Rights are retained by the author(s) and/ or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This item cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder(s). The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hadebe, S., Kirstein, F., Fierens, K., Chen, K., Drummond, R. A., Vautier, S., ... Brown, G. D. (2015). Microbial ligand costimulation drives neutrophilic steroid-refractory asthma. PLoS ONE, 10(8), [e0134219]. https://doi.org/10.1371/journal.pone.0134219