eprintid: 28400
rev_number: 22
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datestamp: 2016-08-23 14:27:52
lastmod: 2021-04-11 07:55:56
status_changed: 2016-08-23 14:27:52
type: article
metadata_visibility: show
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eprint_status: archive
creators_name: Hadebe, S
creators_name: Kirstein, F
creators_name: Fierens, K
creators_name: Chen, K
creators_name: Drummond, RA
creators_name: Vautier, S
creators_name: Sajaniemi, S
creators_name: Murray, G
creators_name: Williams, DL
creators_name: Redelinghuys, P
creators_name: Reinhart, TA
creators_name: Junecko, BAF
creators_name: Kolls, JK
creators_name: Lambrecht, BN
creators_name: Brombacher, F
creators_name: Brown, GD
creators_name: Ryffel, B
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creators_email: koc5@pitt.edu
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creators_email: reinhar@pitt.edu
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creators_id: REINHAR
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contributors_type: http://www.loc.gov/loc.terms/relators/EDT
contributors_name: Ryffel, Bernhard
title: Microbial ligand costimulation drives neutrophilic steroid-refractory asthma
ispublished: pub
divisions: sch_gsph_infectiousdiseasesmicrobiology
divisions: sch_med_Pediatrics
full_text_status: public
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 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.
date: 2015-08-11
date_type: published
publication: PLoS ONE
volume: 10
number: 8
institution: University of Pittsburgh
refereed: TRUE
etd_access_restriction: immediate
etd_patent_pending: FALSE
id_number: 10.1371/journal.pone.0134219
citation:   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).       
document_url: http://d-scholarship-dev.library.pitt.edu/28400/1/journal.pone.0134219.PDF
document_url: http://d-scholarship-dev.library.pitt.edu/28400/3/licence.txt