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.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-16670 |
| Date | 11 August 2015 |
| Creators | 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., Ryffel, Bernhard |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | ETSU Faculty Works |
| Rights | http://creativecommons.org/licenses/by/4.0/ |
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