Microbial Ligand Costimulation Drives Neutrophilic Steroid-Refractory Asthma.
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, des...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0134219&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850125307373158400 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Sabelo Hadebe |
| collection | DOAJ |
| description | 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 microbial 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. |
| format | Article |
| id | doaj-art-64f80bc014614b9eab6e293c96da924b |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-64f80bc014614b9eab6e293c96da924b2025-08-20T02:34:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013421910.1371/journal.pone.0134219Microbial Ligand Costimulation Drives Neutrophilic Steroid-Refractory Asthma.Sabelo HadebeFrank KirsteinKaat FierensKong ChenRebecca A DrummondSimon VautierSara SajaniemiGraeme MurrayDavid L WilliamsPierre RedelinghuysTodd A ReinhartBeth A Fallert JuneckoJay K KollsBart N LambrechtFrank BrombacherGordon D BrownAsthma 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 microbial 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0134219&type=printable |
| spellingShingle | 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 Microbial Ligand Costimulation Drives Neutrophilic Steroid-Refractory Asthma. PLoS ONE |
| title | Microbial Ligand Costimulation Drives Neutrophilic Steroid-Refractory Asthma. |
| title_full | Microbial Ligand Costimulation Drives Neutrophilic Steroid-Refractory Asthma. |
| title_fullStr | Microbial Ligand Costimulation Drives Neutrophilic Steroid-Refractory Asthma. |
| title_full_unstemmed | Microbial Ligand Costimulation Drives Neutrophilic Steroid-Refractory Asthma. |
| title_short | Microbial Ligand Costimulation Drives Neutrophilic Steroid-Refractory Asthma. |
| title_sort | microbial ligand costimulation drives neutrophilic steroid refractory asthma |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0134219&type=printable |
| work_keys_str_mv | AT sabelohadebe microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT frankkirstein microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT kaatfierens microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT kongchen microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT rebeccaadrummond microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT simonvautier microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT sarasajaniemi microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT graememurray microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT davidlwilliams microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT pierreredelinghuys microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT toddareinhart microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT bethafallertjunecko microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT jaykkolls microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT bartnlambrecht microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT frankbrombacher microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma AT gordondbrown microbialligandcostimulationdrivesneutrophilicsteroidrefractoryasthma |