IFN-β is a macrophage-derived effector cytokine facilitating the resolution of bacterial inflammation
| Autor: | Driss El Kebir, Yonatan Feuermann, Amira Othman, Soaad Soboh, Janan Saadi, Neta Peled, Amiram Ariel, Sagie Schif-Zuck, Simaan Assi, Dalit Barkan, Noa Sher, Meriem Sekheri, János G. Filep, Sergei Butenko, Senthil Kumaran Satyanarayanan |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Neutrophils medicine.medical_treatment General Physics and Astronomy Apoptosis 02 engineering and technology Jurkat cells Jurkat Cells Mice Macrophage lcsh:Science Mice Knockout Phagocytes Multidisciplinary Chemistry Effector Middle Aged 021001 nanoscience & nanotechnology 3. Good health Cell biology Cytokine Female medicine.symptom 0210 nano-technology Adult STAT3 Transcription Factor Science Phagocytosis Primary Cell Culture Immunology Inflammation Peritonitis Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Escherichia coli Pneumonia Bacterial medicine Animals Humans Efferocytosis Monocytes and macrophages Aged Gene Expression Profiling Macrophages Interferon-beta General Chemistry Innate immune cells Disease Models Animal 030104 developmental biology lcsh:Q |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The uptake of apoptotic polymorphonuclear cells (PMN) by macrophages is critical for timely resolution of inflammation. High-burden uptake of apoptotic cells is associated with loss of phagocytosis in resolution phase macrophages. Here, using a transcriptomic analysis of macrophage subsets, we show that non-phagocytic resolution phase macrophages express a distinct IFN-β-related gene signature in mice. We also report elevated levels of IFN-β in peritoneal and broncho-alveolar exudates in mice during the resolution of peritonitis and pneumonia, respectively. Elimination of endogenous IFN-β impairs, whereas treatment with exogenous IFN-β enhances, bacterial clearance, PMN apoptosis, efferocytosis and macrophage reprogramming. STAT3 signalling in response to IFN-β promotes apoptosis of human PMNs. Finally, uptake of apoptotic cells promotes loss of phagocytic capacity in macrophages alongside decreased surface expression of efferocytic receptors in vivo. Collectively, these results identify IFN-β produced by resolution phase macrophages as an effector cytokine in resolving bacterial inflammation. Clearance of apoptotic neutrophils by macrophages is important for the resolution of inflammation. Here, the authors show that interferon-β produced by resolution phase macrophages promotes neutrophil apoptosis and efferocytosis and induces macrophage reprogramming to a pro-resolving phenotype, thereby identifying IFN-β as a multi-pronged pro-resolution cytokine. |
| Databáze: | OpenAIRE |
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