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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Marten A HoeksemaMenno P J de Winther

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.

References

May 18, 2000·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·K L O'BrienS F Dowell
Aug 17, 2001·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·M L De BoerA S Cross
Oct 4, 2003·Journal of Leukocyte Biology·Kate SchroderDavid A Hume
Jan 31, 2004·Seminars in Immunology·Kiyoshi Takeda, Shizuo Akira
Jun 4, 2005·Nucleic Acids Research·Shannan J Ho SuiWyeth W Wasserman
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Gordon K Smyth
Aug 22, 2006·Immunobiology·Kate SchroderDavid A Hume
Aug 29, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Johnson RajasinghRaj Kishore
Aug 31, 2006·Methods in Enzymology·Mark Reimers, Vincent J Carey
Oct 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Hideo NegishiKenya Honda
Oct 13, 2006·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Vishwas D JoshiAlan S Cross
May 26, 2007·Nature Reviews. Immunology·Akihiko YoshimuraMasato Kubo
Jun 26, 2007·Bioinformatics·Mark J DunningSimon Tavaré
Sep 4, 2007·Current Opinion in Immunology·Estelle BettelliVijay K Kuchroo
Jan 30, 2008·The Journal of Experimental Medicine·Arnaud DidierlaurentTracy Hussell
May 21, 2008·Proceedings of the National Academy of Sciences of the United States of America·Saebyeol JangRodney W Johnson
Oct 28, 2008·Bioinformatics·J M CairnsA G Lynch
Dec 2, 2008·Cytokine & Growth Factor Reviews·James E McLaren, Dipak P Ramji
Dec 25, 2008·Bioinformatics·Audrey KauffmannWolfgang Huber
Jun 3, 2009·The Journal of Clinical Investigation·Arash ShahangianJane C Deng
Nov 20, 2009·Nucleic Acids Research·Nuno L Barbosa-MoraisSimon Tavaré
Jun 1, 2010·Immunity·Siamon Gordon, Fernando O Martinez
Dec 24, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anupa KudvaJohn F Alcorn
Jan 18, 2011·Nature Immunology·Thomas KrausgruberIrina A Udalova
Feb 9, 2011·Archives of Pediatrics & Adolescent Medicine·Derek J WilliamsSamir S Shah
Mar 13, 2012·Current Atherosclerosis Reports·Marten A HoeksemaMenno P J de Winther
Jan 22, 2013·Cell·Renato OstuniGioacchino Natoli
Sep 10, 2013·Molecular Endocrinology·Susan J BurkeJ Jason Collier
Oct 4, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Keven M RobinsonJohn F Alcorn
Oct 30, 2013·American Journal of Respiratory Cell and Molecular Biology·Miriam H van LieshoutTom van der Poll
Nov 16, 2013·PloS One·Brendon P SciclunaTom van der Poll
Mar 19, 2014·Current Opinion in Immunology·Jessica QuintinMihai G Netea
Mar 29, 2014·F1000prime Reports·Fernando O Martinez, Siamon Gordon
Jul 11, 2014·EMBO Molecular Medicine·Marten A HoeksemaMenno Pj de Winther

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Citations

Mar 8, 2016·Nature Immunology·Shih-Chin ChengMihai G Netea
Oct 30, 2016·Antioxidants & Redox Signaling·Marten A Hoeksema, Menno P de Winther
Oct 6, 2017·Antioxidants & Redox Signaling·Charlotte D C C van der HeijdenSamuel T Keating
Jan 11, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carolina SerranoPorfirio Nava
Feb 1, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Beth T CaruanaKyle L Hoehn
Apr 5, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laurie C EldredgeSteven F Ziegler
Oct 6, 2019·Life Science Alliance·William J CrislerLaurel L Lenz
Feb 24, 2017·Frontiers in Immunology·Gökçe Yıldırım-BuharalıoğluAndrew C Newby
Nov 22, 2019·Frontiers in Nutrition·Gloria SerenaAlessio Fasano
Apr 26, 2017·International Journal of Molecular Medicine·Bing WangMin Li
Mar 9, 2020·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Goutham V Ganesh, Kunka Mohanram Ramkumar
Mar 11, 2020·The Journal of Clinical Investigation·Edy Y KimMichael B Brenner
Mar 27, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fiamma SalernoMonika C Wolkers
Jun 28, 2017·The Journal of Biological Chemistry·Daniel S GreenJulio C Valencia
Jan 8, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaji LiuJeffrey J Saucerman

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