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

Title: Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza
Authors: Dunning, J
Blankley, S
Hoang, LT
Cox, M
Graham, CM
James, PL
Bloom, CI
Chaussabel, D
Banchereau, J
Brett, SJ
Moffatt, MF
O’Garra, A
Openshaw, PJM
Item Type: Journal Article
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.
Issue Date: 18-May-2018
Date of Acceptance: 13-Apr-2018
URI: http://hdl.handle.net/10044/1/60073
DOI: 10.1038/s41590-018-0111-5
ISSN: 1529-2916
Start Page: 625
End Page: 635
Journal / Book Title: Nature Immunology
Volume: 19
Copyright Statement: © 2018 Nature America Inc., part of Springer Nature. All rights reserved.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Wellcome Trust
National Institute for Health Research
Medical Research Council (MRC)
Medical Research Council (MRC)
Wellcome Trust
Funder's Grant Number: 090382/Z/09/Z
090382/Z/09/Z
083567/Z/07/Z
NF-SI-0513-10150
MR/R502121/1
G0902266
096964/Z/11/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
VIRUS-INFECTION
UNITED-KINGDOM
LUNG INJURY
DISEASE
PROCALCITONIN
METAANALYSIS
CIRCULATION
BIOLOGY
MARKERS
HUMANS
Adolescent
Adult
Aged
Biomarkers
Disease Progression
Female
Humans
Influenza, Human
Interferons
Male
Middle Aged
Neutrophils
RNA, Messenger
Transcriptome
Young Adult
MOSAIC Investigators
Neutrophils
Humans
Disease Progression
Interferons
RNA, Messenger
Adolescent
Adult
Aged
Middle Aged
Female
Male
Influenza, Human
Young Adult
Transcriptome
Biomarkers
Immunology
1107 Immunology
Notes: 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.
Publication Status: Published
Appears in Collections:Division of Surgery
National Heart and Lung Institute
Airway Disease
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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