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Title:
IFN-β is a macrophage-derived effector cytokine facilitating the resolution of bacterial inflammation | Nature Communications
Description:
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.
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nature portfolio privacy policy lipophilic fluorochrome chloromethyl-x-rosamine advertising macrophage-derived multi-pronged effector nature communications pe-conjugated anti-f4/80 abs apc-conjugated anti-mouse tim4 anti-ifn-β-treated wt mice specific pathogen-free conditions tlr9-mediated ifn-β production ifn-beta-stat3-dependent pathway anti-ifn-β antibody delayed source data file libraries reprints isotype-matched irrelevant ab phagocytic nature rabbit anti-mouse isg-15 pan-caspase inhibitor q-vd clinical research committee research center pro-resolving cytokine tgf-β percp anti-mouse cd45 apc anti-mouse mertk recombinant mouse ifn-β1 isotype-matched rat igg1 cyclin-dependent kinase inhibitors1 exogenous ifn-β enhances intracellular ifn-β protein pe anti-mouse f4/80 pe-conjugated gr1 antibodies atp-binding cassette a1 anti-ifn-β antibody calcium-dependent proapoptotic effect pro-resolving lipid mediators exogenous ifn-β acts ifn-β directly promotes mouse recombinant ifn-β nature nature 510 nature 484 nature 390 nature 477 nature 416 lipopolysaccharide-induced endotoxin shock nf-kappab signaling pathways endogenous ifn-β impairs research design blocking ifn-β abrogates
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headline:IFN-β is a macrophage-derived effector cytokine facilitating the resolution of bacterial inflammation
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headline:IFN-β is a macrophage-derived effector cytokine facilitating the resolution of bacterial inflammation
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name:Department of Pathology and Cell Biology, University of Montreal, and Research Center, Maisonneuve-Rosemont Hospital, Montreal, Canada
name:Department of Biology and Human Biology, University of Haifa, Haifa, Israel
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