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

Dunning, J. et al. (2018) Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza. Nature Immunology, 19(6), pp. 625-635. (doi: 10.1038/s41590-018-0111-5) (PMID:29777224) (PMCID:PMC5985949)

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.

• Item Type: Articles
• Additional Information: MOSAIC Study was supported by a joint award from the Wellcome Trust and the Medical Research Council (090382/Z/09/Z). The MOSAIC consortium (ClinicalTrials.gov identifier NCT00965354) was supported by UK National Institute for Health Research (NIHR) Comprehensive Local Research Networks (CLRNs), the Biomedical Research Centre (NIHR Imperial BRC) and Unit (NIHR Liverpool BRU), the Health Protection Research Unit in Respiratory Infections in partnership with Public Health England (PHE) at Imperial College London (NIHR HPRU RI), the Health Protection Agency (latterly PHE) Microbiology Services, Colindale and the staff of the Roslin Institute, Edinburgh, Scotland. A.O.G. and C.G. were supported by the Medical Research Council, United Kingdom (U117565642), The Francis Crick Institute, London (AOG10126, which receives its core funding from Cancer Research UK (FC001126)), the UK Medical Research Council (FC001126), the Wellcome Trust (FC001126) and the UK Medical Research Council (MR/ U117565642/1). S.B. was in part jointly funded by the UK Medical Research Council (MRC) as above and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement (MR/J010723/1). C.B. was funded by an MRC CRTF. P.J.M.O. was supported by EU FP7 PREPARE project 602525.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Adamson, Dr Walt
• Authors: Dunning, J., Blankley, S., Hoang, L. T., Cox, M., Graham, C. M., James, P. L., Bloom, C. I., Chaussabel, D., Banchereau, J., Brett, S. J., MOSAIC Investigators, , Moffatt, M. F., O’Garra, A., and Openshaw, P. J. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Nature Immunology
• Publisher: Nature Research
• ISSN: 1529-2908
• ISSN (Online): 1529-2916
• Published Online: 18 May 2018