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

Authors
  • Dunning, Jake1, 2
  • Blankley, Simon3
  • Hoang, Long T1
  • Cox, Mike4
  • Graham, Christine M3
  • James, Philip L4
  • Bloom, Chloe I3
  • Chaussabel, Damien5
  • Banchereau, Jacques6
  • Brett, Stephen J7
  • Moffatt, Miriam F4
  • O'Garra, Anne8
  • Openshaw, Peter J M9
  • 1 Respiratory Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.
  • 2 National Infection Service, Public Health England, London, UK.
  • 3 Laboratory of Immunoregulation & Infection, The Francis Crick Institute, London, UK.
  • 4 Genomic Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
  • 5 Sidra Medical and Research Centre, Doha, Qatar. , (Qatar)
  • 6 The Jackson Laboratory for Genomic Medicine, Farmington, USA.
  • 7 Surgery and Cancer, National Heart and Lung Institute, Imperial College London, London, UK.
  • 8 Laboratory of Immunoregulation & Infection, The Francis Crick Institute, London, UK. [email protected]
  • 9 Respiratory Infection Section, National Heart and Lung Institute, Imperial College London, London, UK. [email protected]
Type
Published Article
Journal
Nature Immunology
Publisher
Springer Nature
Publication Date
Jun 01, 2018
Volume
19
Issue
6
Pages
625–635
Identifiers
DOI: 10.1038/s41590-018-0111-5
PMID: 29777224
Source
Medline
License
Unknown

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.

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