IFN-β is a macrophage-derived effector cytokine facilitating the resolution of bacterial inflammation

Area of Science:

• Immunology
• Cell Biology
• Inflammation Research

Background:

• Macrophage phagocytosis of apoptotic polymorphonuclear cells (PMN) is crucial for resolving inflammation.
• High apoptotic cell burdens can lead to a loss of phagocytic capacity in resolution phase macrophages.

Purpose of the Study:

• To investigate the molecular mechanisms underlying the loss of phagocytosis in resolution phase macrophages.
• To identify the role of Interferon-beta (IFN-β) in the resolution of bacterial inflammation.

Main Methods:

• Transcriptomic analysis of mouse macrophage subsets.
• Measurement of IFN-β levels in peritoneal and broncho-alveolar exudates.
• In vivo and in vitro experiments involving IFN-β manipulation and STAT3 signaling.

Main Results:

• Non-phagocytic resolution phase macrophages exhibit a distinct IFN-β-related gene signature.
• Elevated IFN-β levels were observed during the resolution of peritonitis and pneumonia in mice.
• IFN-β enhances bacterial clearance, PMN apoptosis, efferocytosis, and macrophage reprogramming, while its absence impairs these processes.
• STAT3 signaling mediates IFN-β-induced apoptosis of human PMNs.
• Apoptotic cell uptake leads to reduced macrophage phagocytic capacity and efferocytic receptor expression.

Conclusions:

• Resolution phase macrophages produce IFN-β as an effector cytokine to resolve bacterial inflammation.
• IFN-β plays a critical role in promoting efferocytosis and restoring macrophage function during inflammation resolution.