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

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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 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.
Original languageEnglish
Article numbere0134219
Number of pages17
JournalPloS ONE
Volume10
Issue number8
Early online date11 Aug 2015
DOIs
Publication statusPublished - 11 Aug 2015

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Dermatophagoides Antigens
Glucans
asthma
Pathology
Refractory materials
Allergens
steroids
Pneumonia
Adrenal Cortex Hormones
Asthma
inflammation
Steroids
Ligands
allergens
agonists
lungs
dust mites
glucans
adrenal cortex hormones
Inflammation

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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

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma. / 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.; Fallert Junecko, Beth A. ; Kolls, Jay K.; Lambrecht, Bart N.; Brombacher, Frank; Brown, Gordon D.

In: PloS ONE, Vol. 10, No. 8, e0134219, 11.08.2015.

Research output: Contribution to journalArticle

Hadebe, S, Kirstein, F, Fierens, K, Chen, K, Drummond, RA, Vautier, S, Sajaniemi, S, Murray, G, Williams, DL, Redelinghuys, P, Reinhart, TA, Fallert Junecko, BA, Kolls, JK, Lambrecht, BN, Brombacher, F & Brown, GD 2015, 'Microbial ligand costimulation drives neutrophilic steroid-refractory asthma', PloS ONE, vol. 10, no. 8, e0134219. https://doi.org/10.1371/journal.pone.0134219
Hadebe S, Kirstein F, Fierens K, Chen K, Drummond RA, Vautier S et al. Microbial ligand costimulation drives neutrophilic steroid-refractory asthma. PloS ONE. 2015 Aug 11;10(8). e0134219. https://doi.org/10.1371/journal.pone.0134219
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. ; Fallert Junecko, Beth A. ; Kolls, Jay K. ; Lambrecht, Bart N. ; Brombacher, Frank ; Brown, Gordon D. / Microbial ligand costimulation drives neutrophilic steroid-refractory asthma. In: PloS ONE. 2015 ; Vol. 10, No. 8.
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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 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.",
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