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Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Hadebe, S and Kirstein, F and Fierens, K and Chen, K and Drummond, RA and Vautier, S and Sajaniemi, S and Murray, G and Williams, DL and Redelinghuys, P and Reinhart, TA and Junecko, BAF and Kolls, JK and Lambrecht, BN and Brombacher, F and Brown, GD and Ryffel, B (2015) Microbial ligand costimulation drives neutrophilic steroid-refractory asthma. PLoS ONE, 10 (8).

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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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Hadebe, S
Kirstein, F
Fierens, K
Chen, Kkoc5@pitt.eduKOC5
Drummond, RA
Vautier, S
Sajaniemi, S
Murray, G
Williams, DL
Redelinghuys, P
Reinhart, TAreinhar@pitt.eduREINHAR
Junecko, BAF
Kolls, JK
Lambrecht, BN
Brombacher, F
Brown, GD
Ryffel, B
ContributionContributors NameEmailPitt UsernameORCID
Date: 11 August 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 10
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0134219
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
School of Medicine > Pediatrics
Refereed: Yes
Date Deposited: 23 Aug 2016 14:27
Last Modified: 30 Mar 2021 13:56


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