10.3389/fimmu.2019.02236.s005
Virginia Meda Spaccamela
Virginia Meda
Spaccamela
Rocio G. Valencia
Rocio G.
Valencia
Oleksandr Pastukhov
Oleksandr
Pastukhov
Andrea Duppenthaler
Andrea
Duppenthaler
Matthias S. Dettmer
Matthias S.
Dettmer
Juliane Erb
Juliane
Erb
Urs C. Steiner
Urs C.
Steiner
Sven Hillinger
Sven
Hillinger
Carsten Speckmann
Carsten
Speckmann
Stephan Ehl
Stephan
Ehl
Janine Reichenbach
Janine
Reichenbach
Ulrich Siler
Ulrich
Siler
Image_3_High Levels of IL-18 and IFN-γ in Chronically Inflamed Tissue in Chronic Granulomatous Disease.JPEG
Frontiers
2019
chronic granulomatous disease
hyperinflammation
macrophage priming
macrophage re-priming
IL-18/IFN-γ loop
2019-10-18 07:15:15
Figure
https://frontiersin.figshare.com/articles/figure/Image_3_High_Levels_of_IL-18_and_IFN-_in_Chronically_Inflamed_Tissue_in_Chronic_Granulomatous_Disease_JPEG/10000520
<p>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.</p><p>Objective: To characterize macrophage subsets and cytokine/chemokine signaling loops involved in CGD tissue hyperinflammation.</p><p>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.</p><p>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.</p><p>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.</p>