Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence

PLoS Pathogens
Cameron R CunninghamDavid G Brooks

Abstract

Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV) to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs) during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I) then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation ...Continue Reading

References

Dec 1, 1993·The Journal of Experimental Medicine·J L FlynnB R Bloom
Mar 23, 2001·Nature Immunology·A V Gett, P D Hodgkin
May 20, 2006·The Journal of Clinical Investigation·David G BrooksMichael B A Oldstone
Oct 13, 2006·The Journal of Experimental Medicine·Mette EjrnaesMatthias G von Herrath
Oct 17, 2006·Nature Medicine·David G BrooksMichael B A Oldstone
Jan 24, 2007·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Lynn AverillNitin J Karandikar
Sep 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shawn D BlackburnE John Wherry
Feb 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sebastien F EmonetJuan C de la Torre
Apr 13, 2010·Current Opinion in Immunology·Laura M Fahey, David G Brooks
Jul 9, 2011·Nature Immunology·E John Wherry
Mar 27, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jonathan M ClinganMehrdad Matloubian
Aug 16, 2012·Proceedings of the National Academy of Sciences of the United States of America·Cherie T Ng, Michael B A Oldstone
Feb 6, 2013·Current Opinion in HIV and AIDS·Delphine SauceVictor Appay
Mar 27, 2013·The Journal of Experimental Medicine·Bernd H ZinselmeyerDorian B McGavern
Apr 13, 2013·Science·John R TeijaroMichael B A Oldstone
Jun 12, 2013·Nucleic Acids Research·Daniel D'AndreaAnna Tramontano
Jun 19, 2013·Immunological Reviews·Elizabeth Miller, Nina Bhardwaj
Jul 9, 2013·Trends in Immunology·Elodie Segura, Sebastian Amigorena
Jul 31, 2013·Immunity·Greg T Motz, George Coukos
Nov 19, 2013·PLoS Pathogens·Kirsten RichterAnnette Oxenius
Jun 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Vineeth VaranasiAlexander V Chervonsky
Sep 28, 2014·Bioinformatics·Simon AndersWolfgang Huber
Jan 17, 2015·Annual Review of Immunology·Carla V RothlinSourav Ghosh
Jan 24, 2015·Nature Reviews. Immunology·Finlay McNabAnne O'Garra
Mar 17, 2015·Current Opinion in Immunology·Laura M Snell, David G Brooks
Mar 22, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jo Marie Tran JancoKeith L Knutson

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Citations

Feb 12, 2017·Trends in Molecular Medicine·Ans De BeuckelaerStefaan De Koker
Sep 21, 2018·Frontiers in Immunology·Diana LlopizPablo Sarobe
Mar 29, 2020·Immunity, Inflammation and Disease·Isabel BarnstorfAnnette Oxenius
Jun 28, 2019·Frontiers in Immunology·Enrique Martin-Gayo, Xu G Yu
Feb 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Heidi J ElsaesserDavid G Brooks
Sep 4, 2020·The Journal of Experimental Medicine·Bethany L MacleodDavid G Brooks
Dec 3, 2020·Annual Review of Pathology·Giselle M BoukhaledDavid G Brooks
Feb 12, 2021·Cancer Science·Sho HangaiHideyuki Yanai

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Methods Mentioned

BETA
RNA-seq
transgenic
ELISA
Assay
flow cytometry
Polymerase Chain Reaction
PCR
Illumina Sequencing

Software Mentioned

HTSeq
GraphPad Prism
R ‘ stats ’ package
TopHat
R package ‘ ggplot2 ’
Functional Interpretation of Differential Expression Analysis ...
Illumina Sequencing Analysis Viewer ( SAV )
R Core Team

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