Document Type
Article
Publication Date
8-11-2015
Description
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. 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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Citation Information
Hadebe, Sabelo; Kirstein, Frank; Fierens, Kaat; Chen, Kong; Drummond, Rebecca A.; Vautier, Simon; Sajaniemi, Sara; Murray, Graeme; Williams, David L.; Redelinghuys, Pierre; Reinhart, Todd A.; Junecko, Beth A.Fallert; Kolls, Jay K.; Lambrecht, Bart N.; Brombacher, Frank; Brown, Gordon D.; and Ryffel, Bernhard. 2015. Microbial Ligand Costimulation Drives Neutrophilic Steroid-Refractory Asthma. PLoS ONE. Vol.10(8). https://doi.org/10.1371/journal.pone.0134219 PMID: 26261989
Copyright Statement
© 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