Meda Spaccamela, Virginia; Valencia, Rocio G; Pastukhov, Oleksandr; Duppenthaler, Andrea; Dettmer, Matthias S.; Erb, Juliane; Steiner, Urs C; Hillinger, Sven; Speckmann, Carsten; Ehl, Stephan; Reichenbach, Janine; Siler, Ulrich (2019). High Levels of IL-18 and IFN-γ in Chronically Inflamed Tissue in Chronic Granulomatous Disease. Frontiers in immunology, 10, p. 2236. Frontiers Research Foundation 10.3389/fimmu.2019.02236
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Background: Chronic granulomatous disease (CGD) is caused by a malfunctioning nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex in phagocytes, leading to impaired bacterial and fungal killing and hyperinflammation. Objective: To characterize macrophage subsets and cytokine/chemokine signaling loops involved in CGD tissue hyperinflammation. Methods: Cytokine/chemokine production and surface marker expression were analyzed in inflamed tissue of four CGD patients and compared to cytokine/chemokine released by CGD macrophages upon priming to different macrophage subpopulations. Furthermore, the re-priming capacity of CGD pro-inflammatory M1 to M2a anti-inflammatory macrophages was evaluated. Results: In human CGD inflammatory tissue, IL-18 and IFN-γ were detected in significant quantity. Immunofluorescence analysis identified macrophages as one source of IL-18 in inflamed tissue. In vitro, CGD macrophages could be primed and re-primed into all inflammatory/anti-inflammatory macrophage subpopulations. IL-18 was also released by M1 CGD and control macrophages. Conclusion: CGD pro-inflammatory M1 macrophages remain M1 primed in vivo. As CGD M1 macrophages can be re-primed to anti-inflammatory M2a phenotype in vitro, macrophages are kept in M1 state in vivo by a persistent pro-inflammatory environment. Our results suggest a paracrine signaling loop between M1 macrophage derived IL-18 and non-macrophage derived IFN-γ maintaining macrophage pro-inflammatory activity in CGD tissue.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine 04 Faculty of Medicine > Service Sector > Institute of Pathology 04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology |
UniBE Contributor: |
Duppenthaler, Andrea, Dettmer, Matthias |
Subjects: |
600 Technology > 610 Medicine & health 500 Science > 570 Life sciences; biology |
ISSN: |
1664-3224 |
Publisher: |
Frontiers Research Foundation |
Language: |
English |
Submitter: |
Anette van Dorland |
Date Deposited: |
11 Nov 2019 12:12 |
Last Modified: |
05 Dec 2022 15:32 |
Publisher DOI: |
10.3389/fimmu.2019.02236 |
PubMed ID: |
31681257 |
Uncontrolled Keywords: |
IL-18/IFN-γ loop chronic granulomatous disease hyperinflammation macrophage priming macrophage re-priming |
BORIS DOI: |
10.7892/boris.134629 |
URI: |
https://boris.unibe.ch/id/eprint/134629 |
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