Viral infection of human lung macrophages increases PDL1 expression via IFNβ

PloS One
Karl J StaplesTom M A Wilkinson

Abstract

Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM) and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in ...Continue Reading

References

Jan 30, 1992·The New England Journal of Medicine·D S RobinsonA B Kay
Feb 1, 1990·The American Review of Respiratory Disease·Y Sibille, H Y Reynolds
Jan 1, 1982·Journal of Medical Virology·B C Rodgers, C A Mims
Feb 12, 1999·Respiration; International Review of Thoracic Diseases·L P Nicod
Aug 10, 1999·Lancet·L P Nicod
Mar 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicole Selenko-GebauerJohannes Stöckl
May 4, 2004·Nature Reviews. Immunology·Lieping Chen
Jun 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Koenraad F van der SluijsTom van der Poll
Mar 18, 2005·Annual Review of Immunology·Rebecca J GreenwaldArlene H Sharpe
Mar 23, 2005·The Journal of Experimental Medicine·Peter A B WarkDonna E Davies
Aug 15, 2006·Nature Medicine·Marco ContoliSebastian L Johnston
Apr 17, 2007·Current Opinion in Immunology·Mary E KeirArlene H Sharpe
Jun 15, 2007·Seminars in Immunology·Eric J SundbergRoy A Mariuzza
Oct 9, 2007·The Journal of Pharmacology and Experimental Therapeutics·Susan J TudhopeLouise E Donnelly
Jul 25, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Adriano BoassoGene M Shearer
Sep 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Simon D MessageSebastian L Johnston
Nov 10, 2009·The European Respiratory Journal·A E TaylorL E Donnelly
Sep 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Zong-Mei ShengJeffery K Taubenberger
Dec 3, 2011·Science Translational Medicine·Shoba AmarnathDaniel H Fowler
Jun 5, 2012·The Journal of Allergy and Clinical Immunology·Annemarie SykesSebastian L Johnston
Jul 17, 2012·The Journal of Clinical Investigation·John J EricksonJohn V Williams
Sep 18, 2012·The Journal of Allergy and Clinical Immunology·Karl J StaplesRatko Djukanović

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Citations

Mar 16, 2016·American Journal of Respiratory and Critical Care Medicine·Jeffrey L Curtis
Oct 31, 2015·American Journal of Respiratory and Critical Care Medicine·Richard T McKendryTom M A Wilkinson
Mar 10, 2012·Physiology & Behavior·John A Kennard, Diana S Woodruff-Pak
Jul 27, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erin D LucasBeth A Jirón Tamburini
Jul 1, 2017·European Respiratory Review : an Official Journal of the European Respiratory Society·Tom M A Wilkinson
Aug 29, 2019·American Journal of Respiratory and Critical Care Medicine·Alastair WatsonTom Wilkinson
May 10, 2020·Journal of Leukocyte Biology·Yong-Hong ZhangGil Mor
May 13, 2020·Immunity, Inflammation and Disease·Julia KölleSusetta Finotto
Mar 12, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jiatao LiuGuoping Sun
May 7, 2019·Frontiers in Immunology·Eduardo I TognarelliPablo A González
Jul 3, 2019·Frontiers in Cellular and Infection Microbiology·Günther Schönrich, Martin J Raftery
Aug 17, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Atul K VermaKeer Sun
Dec 19, 2018·Frontiers in Immunology·Martin J RafteryGünther Schönrich
Aug 7, 2018·Frontiers in Immunology·Grace E CooperKarl J Staples
Nov 11, 2020·Expert Review of Respiratory Medicine·Katerina ByanovaLaurence Huang
Mar 23, 2021·Therapeutic Advances in Respiratory Disease·Alastair Watson, Tom M A Wilkinson
Jun 3, 2021·International Journal of Molecular Sciences·Hadia FarrukhKaren Mossman
Jun 28, 2021·Reviews in Medical Virology·Goutham V Ganesh, Ramkumar K Mohanram
Aug 21, 2021·European Respiratory Review : an Official Journal of the European Respiratory Society·H Burke, T M A Wilkinson
Sep 10, 2021·Frontiers in Cellular and Infection Microbiology·Jodie AcklandKarl J Staples

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Methods Mentioned

BETA
flow cytometry
Flow
FACS
PCR
ELISA
Assay
dot blot
transfection

Software Mentioned

GraphPad
FACSDiva
GraphPad Prism

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