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

Senthil Kumaran Satyanarayanan, Driss El Kebir, Soaad Soboh, Sergei Butenko, Meriem Sekheri, Janan Saadi, Neta Peled, Simaan Assi, Amira Othman, Sagie Schif-Zuck, Yonatan Feuermann, Dalit Barkan, Noa Sher, János G. Filep, Amiram Ariel

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number3471
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus subject areas

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

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