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

Marten A. Hoeksema, Brendon P. Scicluna, Marieke C.S. Boshuizen, Saskia Van Der Velden, Annette E. Neele, Jan Van Den Bossche, Hanke L. Matlung, Timo K. Van Den Berg, Pieter Goossens, Menno P.J. De Winther*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)3909-3916
Number of pages8
JournalJournal of Immunology
Volume194
Issue number8
DOIs
Publication statusPublished - 1 Jan 2015

Cite this

Hoeksema, M. A., Scicluna, B. P., Boshuizen, M. C. S., Van Der Velden, S., Neele, A. E., Van Den Bossche, J., ... De Winther, M. P. J. (2015). IFN-γ priming of macrophages represses a part of the inflammatory program and attenuates neutrophil recruitment. Journal of Immunology, 194(8), 3909-3916. https://doi.org/10.4049/jimmunol.1402077