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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1111/all.14535
Journal or Publication Title: Allergy
Date: 2020
Divisions: UTS Centre for Inflammation
Depositing User: General Admin
Identification Number: 10.1111/all.14535
ISSN: 0105-4538
Date Deposited: 03 Jan 2021 23:52
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.

Creators:
Creators
Email
Tiotiu, Angelica
UNSPECIFIED
Zounemat Kermani, Nazanin
UNSPECIFIED
Badi, Yusef
UNSPECIFIED
Pavlidis, Stelios
UNSPECIFIED
Hansbro, Philip M.
UNSPECIFIED
Guo, Yi‐Ke
UNSPECIFIED
Chung, Kian Fan
UNSPECIFIED
Adcock, Ian M.
UNSPECIFIED
Last Modified: 03 Jan 2021 23:52
URI: https://eprints.centenary.org.au/id/eprint/834

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