Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza

Nature Immunology
Jake DunningMOSAIC Investigators

Abstract

Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data were obtained by MOSAIC investigators. Signatures reflective of interferon-related antiviral pathways were common up to day 4 of symptoms in patients who did not require mechanical ventilator support; in those who needed mechanical ventilation, an inflammatory, activated-neutrophil and cell-stress or death ('bacterial') pattern was seen, even early in disease. Identifiable bacterial co-infection was not necessary for this 'bacterial' signature but was able to enhance its development while attenuating the early 'viral' signature. Our findings emphasize the importance of timing and severity in the interpretation of host responses to acute viral infection and identify specific patterns of immune-system activation that might enable the development of novel diagnostic and therapeutic tools for severe influenza.

Associated Clinical Trials

References

Jun 7, 2003·BMJ : British Medical Journal·Klaus Stöhr
Aug 13, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Liliana SimonJacques Lacroix
Nov 25, 2006·Critical Care : the Official Journal of the Critical Care Forum·John C Marshall
Jun 23, 2009·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Michael J CarrWilliam W Hall
Oct 30, 2009·Trends in Immunology·Joseph Sriyal Malik PeirisJohn Malcolm Nicholls
Dec 22, 2009·Chest·David S HuiPaul K S Chan
Mar 3, 2010·Annual Review of Immunology·Virginia PascualJacques Banchereau
May 7, 2010·The New England Journal of Medicine·Edgar BautistaKarl G Nicholson
Jul 16, 2010·Thorax·J S Nguyen-Van-TamUNKNOWN Influenza Clinical Information Network (FLU-CIN)
Apr 13, 2011·Immunology and Cell Biology·Michelle D TateJustine D Mintern
Jun 28, 2011·The American Journal of Pathology·Teluguakula NarasarajuVincent T Chow
Jul 12, 2011·Nature Immunology·Helder I NakayaBali Pulendran
Mar 7, 2012·Microbiology and Molecular Biology Reviews : MMBR·Jennifer R TisoncikMichael G Katze
Mar 27, 2012·Nature·Aaron R EverittPaul Kellam
May 11, 2013·The Journal of Infectious Diseases·Ann R FalseyEdward E Walsh
Jun 29, 2013·Current Opinion in Virology·Peter J Openshaw, Christopher Chiu
Nov 19, 2013·The Lancet Infectious Diseases·Kirsty R ShortThijs Kuiken
Apr 11, 2014·The Lancet. Respiratory Medicine·Andrew C HaywardUNKNOWN Flu Watch Group
May 14, 2014·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Simon BlankleyAnne O'Garra
May 23, 2014·Nature Communications·Sophia DavidsonAndreas Wack
Jan 24, 2015·Nature Reviews. Immunology·Finlay McNabAnne O'Garra
Sep 27, 2015·American Journal of Physiology. Lung Cellular and Molecular Physiology·David J Gregory, Lester Kobzik

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Citations

Feb 23, 2019·Viruses·Ashley A StegelmeierKhalil Karimi
Jul 17, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chuanxin LiuWeisan Chen
Sep 4, 2019·Der Internist·C Malainou, S Herold
Feb 28, 2020·European Journal of Immunology·Mirae ParkPeter J M Openshaw
Jan 9, 2020·Intensive Care Medicine·Antoni TorresNelson Lee
Jun 5, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Judy ChenDaniel R Goldstein
Sep 29, 2020·Immunological Investigations·Parisa LotfinejadBehzad Baradaran
Jan 27, 2019·PLoS Pathogens·Giovanny J Martínez-ColónBethany B Moore
Jul 26, 2019·Science Translational Medicine·Jeffery K TaubenbergerDavid M Morens
Aug 19, 2020·Nature Medicine·Adam G LaingAdrian C Hayday
Sep 12, 2019·Frontiers in Cellular and Infection Microbiology·Alba LlibreDarragh Duffy
Jun 26, 2020·Frontiers in Pharmacology·Teluguakula NarasarajuMarko Radic
May 20, 2018·Nature Immunology·David F Tough
Aug 9, 2019·The European Respiratory Journal·Akhilesh JhaPeter J Openshaw
Apr 26, 2019·Intensive Care Medicine·Benjamin M TangAnthony S McLean
Mar 7, 2020·Nature Communications·Michael B MayhewTimothy E Sweeney
Apr 23, 2020·Mucosal Immunology·Jake DunningPeter J M Openshaw
Apr 5, 2020·The Journal of Infectious Diseases·Jurre Y SiegersKirsty R Short
Oct 10, 2020·Science·Maximillian S HabibiPeter J M Openshaw
Dec 12, 2020·ELife·Brendon P SciclunaUNKNOWN Molecular Diagnosis and Risk Stratification in Sepsis (MARS) consortium
Jul 28, 2020·The Journal of Allergy and Clinical Immunology·Akhilesh JhaPeter J M Openshaw
Jan 15, 2021·Genome Medicine·Anna C AschenbrennerUNKNOWN German COVID-19 Omics Initiative (DeCOI)
Dec 20, 2020·Scientific Reports·Nicholas ParkinsonSara Clohisey
Aug 12, 2020·European Journal of Immunology·Mirae ParkPeter J M Openshaw
Jul 30, 2019·Clinical Therapeutics·Melissa H RossEphraim L Tsalik
Mar 25, 2021·Mucosal Immunology·Cecilia Johansson, Freja C M Kirsebom
Mar 12, 2021·Science Immunology·Ryan S ThwaitesUNKNOWN ISARIC4C investigators
May 26, 2021·Proceedings of the National Academy of Sciences of the United States of America·Julia di IulioAmalio Telenti

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Datasets Mentioned

BETA
GSE111368

Methods Mentioned

BETA
PCR
bronchoalveolar lavage

Clinical Trials Mentioned

NCT00965354

Software Mentioned

CIN
Flu
Ingenuity
GraphPad
GeneSpring GX
GeneSpring GX12
IPA
GraphPad Prism
Excel
MOSAIC

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