Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

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dc.contributor.authorHadebe, Sabeloen_ZA
dc.contributor.authorKirstein, Franken_ZA
dc.contributor.authorFierens, Kaaten_ZA
dc.contributor.authorChen, Kongen_ZA
dc.contributor.authorDrummond, Rebecca Aen_ZA
dc.contributor.authorVautier, Simonen_ZA
dc.contributor.authorSajaniemi, Saraen_ZA
dc.contributor.authorMurray, Graemeen_ZA
dc.contributor.authorWilliams, David Len_ZA
dc.contributor.authorRedelinghuys, Pierreen_ZA
dc.contributor.authorReinhart, Todd Aen_ZA
dc.contributor.authorJunecko, Beth A Fallerten_ZA
dc.contributor.authorKolls, Jay Ken_ZA
dc.contributor.authorLambrecht, Bart Nen_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.contributor.authorBrown, Gordon Den_ZA
dc.date.accessioned2016-02-10T14:46:22Z
dc.date.available2016-02-10T14:46:22Z
dc.date.issued2015en_ZA
dc.description.abstractAsthma 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.en_ZA
dc.identifier.apacitationHadebe, S., Kirstein, F., Fierens, K., Chen, K., Drummond, R. A., Vautier, S., ... Brown, G. D. (2015). Microbial ligand costimulation drives neutrophilic steroid-refractory asthma. <i>PLoS One</i>, http://hdl.handle.net/11427/16945en_ZA
dc.identifier.chicagocitationHadebe, Sabelo, Frank Kirstein, Kaat Fierens, Kong Chen, Rebecca A Drummond, Simon Vautier, Sara Sajaniemi, et al "Microbial ligand costimulation drives neutrophilic steroid-refractory asthma." <i>PLoS One</i> (2015) http://hdl.handle.net/11427/16945en_ZA
dc.identifier.citationHadebe, S., Kirstein, F., Fierens, K., Chen, K., Drummond, R. A., Vautier, S., ... & Reinhart, T. A. (2015). Microbial ligand costimulation drives neutrophilic steroid-refractory asthma. PloS one, 10(8), e0134219. doi:10.1371/journal.pone.0134219en_ZA
dc.identifier.ris TY - Journal Article AU - Hadebe, Sabelo AU - Kirstein, Frank AU - Fierens, Kaat AU - Chen, Kong AU - Drummond, Rebecca A AU - Vautier, Simon AU - Sajaniemi, Sara AU - Murray, Graeme AU - Williams, David L AU - Redelinghuys, Pierre AU - Reinhart, Todd A AU - Junecko, Beth A Fallert AU - Kolls, Jay K AU - Lambrecht, Bart N AU - Brombacher, Frank AU - Brown, Gordon D AB - 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. DA - 2015 DB - OpenUCT DO - 10.1371/journal.pone.0134219 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Microbial ligand costimulation drives neutrophilic steroid-refractory asthma TI - Microbial ligand costimulation drives neutrophilic steroid-refractory asthma UR - http://hdl.handle.net/11427/16945 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0134219en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16945
dc.identifier.vancouvercitationHadebe S, Kirstein F, Fierens K, Chen K, Drummond RA, Vautier S, et al. Microbial ligand costimulation drives neutrophilic steroid-refractory asthma. PLoS One. 2015; http://hdl.handle.net/11427/16945.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.en_ZA
dc.rights.holder© 2015 Hadebe et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherInflammationen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherAsthmaen_ZA
dc.subject.otherMouse modelsen_ZA
dc.subject.otherNeutrophilsen_ZA
dc.subject.otherInflammatory diseasesen_ZA
dc.subject.otherCloningen_ZA
dc.titleMicrobial ligand costimulation drives neutrophilic steroid-refractory asthmaen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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