- Title
- Sputum macrophage diversity and activation in asthma: Role of severity and inflammatory phenotype
- Creator
- Tiotiu, Angelica; Zounemat Kermani, Nazanin; Badi, Yusef; Pavlidis, Stelios; Hansbro, Philip M.; Guo, Yi-Ke; Chung, Kian Fan; Adcock, Ian M.
- Relation
- Allergy: European Journal of Allergy and Clinical Immunology Vol. 76, Issue 3, p. 775-788
- Publisher Link
- http://dx.doi.org/10.1111/all.14535
- Publisher
- Wiley-Blackwell
- Resource Type
- journal article
- Date
- 2021
- Description
- 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.
- Subject
- asthma; gene set variation analysis; macrophage subtypes; sputum; tissue-resident; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1461951
- Identifier
- uon:46346
- Identifier
- ISSN:0105-4538
- Rights
- This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors.
- Language
- eng
- Full Text
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