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Multi-omics links I...
Multi-omics links IL-6 trans-signalling with neutrophil extracellular trap formation and Haemophilus infection in COPD
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Winslow, S. (author)
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Odqvist, L. (author)
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Diver, S. (author)
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Riise, R. (author)
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Abdillahi, S. (author)
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Wingren, C. (author)
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Lindmark, H. (author)
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Wellner, A. (author)
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Lundin, S. (author)
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Yrlid, L. (author)
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- Ax, Elisabeth (author)
- Gothenburg University,Göteborgs universitet,Krefting Research Centre
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Djukanovic, R. (author)
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Sridhar, S. (author)
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Higham, A. (author)
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Singh, D. (author)
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Southworth, T. (author)
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Brightling, C. E. (author)
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Olsson, H. K. (author)
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Jevnikar, Z. (author)
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(creator_code:org_t)
- 2021-03-25
- 2021
- English.
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 58:4
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https://doi.org/10.1...
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Abstract
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- Background: Interleukin (IL)-6 trans-signalling (IL-6TS) is emerging as a pathogenic mechanism in chronic respiratory diseases; however, the drivers of IL-6TS in the airways and the phenotypic characteristic of patients with increased IL-6TS pathway activation remain poorly understood. Objective: Our aim was to identify and characterise COPD patients with increased airway IL-6TS and to elucidate the biological drivers of IL-6TS pathway activation. Methods: We used an IL-6TS-specific sputum biomarker profile (soluble IL-6 receptor (sIL-6R), IL-6, IL1 beta, IL-8, macrophage inflammatory protein-1 beta) to stratify sputum data from patients with COPD (n=74; Biomarkers to Target Antibiotic and Systemic Corticosteroid Therapy in COPD Exacerbation (BEAT-COPD)) by hierarchical clustering. The IL-6TS signature was related to clinical characteristics and sputum microbiome profiles. The induction of neutrophil extracellular trap formation (NETosis) and IL-6TS by Haemophilus influenzae were studied in human neutrophils. Results: Hierarchical clustering revealed an IL-6TS-high subset (n=24) of COPD patients, who shared phenotypic traits with an IL-6TS-high subset previously identified in asthma. The subset was characterised by increased sputum cell counts (p=0.0001), persistent sputum neutrophilia (p=0.0004), reduced quality of life (Chronic Respiratory Questionnaire total score; p=0.008), and increased levels of pro-inflammatory mediators and matrix metalloproteinases in sputum. IL-6TS-high COPD patients showed an increase in Proteobacteria, with Haemophilus as the dominating genus. NETosis induced by H. influenzae was identified as a potential mechanism for increased sIL-6R levels. This was supported by a significant positive correlation between sIL-6R and NETosis markers in bronchoalveolar lavage fluid from COPD patients. Conclusion: IL-6TS pathway activation due to chronic colonisation with Haemophilus may be an important disease driver in a subset of COPD patients.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Keyword
- obstructive pulmonary-disease
- chromatin decondensation
- influenzae
- endotoxin
- receptor
- expression
- inflammation
- responses
- severity
- netosis
- genes
- Respiratory System
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Winslow, S.
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Odqvist, L.
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Diver, S.
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Riise, R.
-
Abdillahi, S.
-
Wingren, C.
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show more...
-
Lindmark, H.
-
Wellner, A.
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Lundin, S.
-
Yrlid, L.
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Ax, Elisabeth
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Djukanovic, R.
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Sridhar, S.
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Higham, A.
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Singh, D.
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Southworth, T.
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Brightling, C. E ...
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Olsson, H. K.
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Jevnikar, Z.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Respiratory Medi ...
- Articles in the publication
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European Respira ...
- By the university
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University of Gothenburg