IFN-γ priming of macrophages represses a part of the inflammatory program and attenuates neutrophil recruitment

J Immunol. 2015 Apr 15;194(8):3909-16. doi: 10.4049/jimmunol.1402077. Epub 2015 Mar 6.


Macrophages form a heterogeneous population of immune cells, which is critical for both the initiation and resolution of inflammation. They can be skewed to a proinflammatory subtype by the Th1 cytokine IFN-γ and further activated with TLR triggers, such as LPS. In this work, we investigated the effects of IFN-γ priming on LPS-induced gene expression in primary mouse macrophages. Surprisingly, we found that IFN-γ priming represses a subset of LPS-induced genes, particularly genes involved in cellular movement and leukocyte recruitment. We found STAT1-binding motifs enriched in the promoters of these repressed genes. Furthermore, in the absence of STAT1, affected genes are derepressed. We also observed epigenetic remodeling by IFN-γ priming on enhancer or promoter sites of repressed genes, which resulted in less NF-κB p65 recruitment to these sites without effects on global NF-κB activation. Finally, the epigenetic and transcriptional changes induced by IFN-γ priming reduce neutrophil recruitment in vitro and in vivo. Our data show that IFN-γ priming changes the inflammatory repertoire of macrophages, leading to a change in neutrophil recruitment to inflammatory sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cell Movement / immunology*
  • Epigenesis, Genetic / drug effects
  • Epigenesis, Genetic / immunology*
  • Female
  • Inflammation / immunology
  • Interferon-gamma / immunology*
  • Lipopolysaccharides / pharmacology
  • Macrophages / immunology*
  • Mice
  • Mice, Knockout
  • Neutrophils / immunology*
  • Response Elements / immunology
  • STAT1 Transcription Factor / immunology
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / immunology
  • Transcription Factor RelA / immunology


  • Lipopolysaccharides
  • Rela protein, mouse
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Toll-Like Receptors
  • Transcription Factor RelA
  • Interferon-gamma

Associated data

  • GEO/GSE60290