Sputum macrophage diversity and activation in asthma: role of severity and inflammatory phenotype

Hansbro, P; Tiotiu, A; Zounemat-Kermani, N; Badi, Y; Pavlidis, S; Chung, KF; Adcock, I

Sputum macrophage diversity and activation in asthma: role of severity and inflammatory phenotype

Hansbro, P

Tiotiu, A Zounemat-Kermani, N Badi, Y Pavlidis, S Chung, KF Adcock, I

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Publisher:: WILEY
Publication Type:: Journal Article
Citation:: Allergy, 2020, (accepted 28.6.20)
Issue Date:: 2020

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Field	Value	Language
dc.contributor.author	Hansbro, P https://orcid.org/0000-0002-4741-3035
dc.contributor.author	Tiotiu, A
dc.contributor.author	Zounemat-Kermani, N
dc.contributor.author	Badi, Y
dc.contributor.author	Pavlidis, S
dc.contributor.author	Chung, KF
dc.contributor.author	Adcock, I
dc.date.accessioned	2020-12-22T23:12:46Z
dc.date.available	2020-06-27
dc.date.available	2020-12-22T23:12:46Z
dc.date.issued	2020
dc.identifier.citation	Allergy, 2020, (accepted 28.6.20)
dc.identifier.issn	0105-4538
dc.identifier.issn	1398-9995
dc.identifier.uri	http://hdl.handle.net/10453/144919
dc.description.abstract	BACKGROUND:Macrophages control innate and acquired immunity, but their role in severe asthma remains ill-defined. We investigated gene signatures of macrophage subtypes in the sputum of 104 asthmatics and 16 healthy volunteers from the U-BIOPRED cohort. METHODS:Forty-nine gene signatures (modules) for differentially stimulated macrophages, one to assess lung tissue-resident cells (TR-Mφ) and two for their polarization (classically and alternatively activated macrophages: M1 and M2, respectively) were studied using gene set variation analysis. We calculated enrichment scores (ES) across severity and previously identified asthma transcriptome-associated clusters (TACs). RESULTS:Macrophage numbers were significantly decreased in severe asthma compared to mild-moderate asthma and healthy volunteers. The ES for most modules were also significantly reduced in severe asthma except for 3 associated with inflammatory responses driven by TNF and Toll-like receptors via NF-κB, eicosanoid biosynthesis via the lipoxygenase pathway and IL-2 biosynthesis (all P < .01). Sputum macrophage number and the ES for most macrophage signatures were higher in the TAC3 group compared to TAC1 and TAC2 asthmatics. However, a high enrichment was found in TAC1 for 3 modules showing inflammatory pathways linked to Toll-like and TNF receptor activation and arachidonic acid metabolism (P < .001) and in TAC2 for the inflammasome and interferon signalling pathways (P < .001). Data were validated in the ADEPT cohort. Module analysis provides additional information compared to conventional M1 and M2 classification. TR-Mφ were enriched in TAC3 and associated with mitochondrial function. CONCLUSIONS:Macrophage activation is attenuated in severe granulocytic asthma highlighting defective innate immunity except for specific subsets characterized by distinct inflammatory pathways.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	WILEY
dc.relation.ispartof	Allergy
dc.relation.isbasedon	10.1111/all.14535
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology
dc.subject.classification	Allergy
dc.title	Sputum macrophage diversity and activation in asthma: role of severity and inflammatory phenotype
dc.type	Journal Article
utslib.citation.volume	(accepted 28.6.20)
utslib.location.activity	Denmark
utslib.for	1107 Immunology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2020-12-22T23:12:33Z
pubs.publication-status	Published
pubs.volume	(accepted 28.6.20)

Abstract:

BACKGROUND:Macrophages control innate and acquired immunity, but their role in severe asthma remains ill-defined. We investigated gene signatures of macrophage subtypes in the sputum of 104 asthmatics and 16 healthy volunteers from the U-BIOPRED cohort. METHODS:Forty-nine gene signatures (modules) for differentially stimulated macrophages, one to assess lung tissue-resident cells (TR-Mφ) and two for their polarization (classically and alternatively activated macrophages: M1 and M2, respectively) were studied using gene set variation analysis. We calculated enrichment scores (ES) across severity and previously identified asthma transcriptome-associated clusters (TACs). RESULTS:Macrophage numbers were significantly decreased in severe asthma compared to mild-moderate asthma and healthy volunteers. The ES for most modules were also significantly reduced in severe asthma except for 3 associated with inflammatory responses driven by TNF and Toll-like receptors via NF-κB, eicosanoid biosynthesis via the lipoxygenase pathway and IL-2 biosynthesis (all P < .01). Sputum macrophage number and the ES for most macrophage signatures were higher in the TAC3 group compared to TAC1 and TAC2 asthmatics. However, a high enrichment was found in TAC1 for 3 modules showing inflammatory pathways linked to Toll-like and TNF receptor activation and arachidonic acid metabolism (P < .001) and in TAC2 for the inflammasome and interferon signalling pathways (P < .001). Data were validated in the ADEPT cohort. Module analysis provides additional information compared to conventional M1 and M2 classification. TR-Mφ were enriched in TAC3 and associated with mitochondrial function. CONCLUSIONS:Macrophage activation is attenuated in severe granulocytic asthma highlighting defective innate immunity except for specific subsets characterized by distinct inflammatory pathways.

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http://hdl.handle.net/10453/144919