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

Collapse authors list.
Dunning, J, Blankley, S, Hoang, LT, Cox, M, Graham, CM, James, PL, Bloom, CI, Chaussabel, D, Banchereau, J, Brett, SJ et al (show 42 more authors) , Moffatt, MF, Habibi, MS, Johnston, SL, Hansel, TT, Levin, M, Thwaites, RS, Warner, JO, Cookson, WO, Gazzard, BG, Hay, A, McCauley, J, Aylin, P, Ashby, D, Barclay, WS, Elderfield, RA, Nadel, S, Herberg, JA, Drumright, LN, Garcia-Alvarez, L, Holmes, AH, Kon, OM, Aston, SJ ORCID: 0000-0002-0701-8364, Gordon, SB, Hussell, T, Thompson, C, Zambon, MC, Baillie, KJ, Hume, DA, Simmonds, P, Hayward, A, Smyth, RL, McNamara, PS ORCID: 0000-0002-7055-6034, Semple, MG ORCID: 0000-0001-9700-0418, Nguyen-Van-Tam, JS, Ho, LP, McMichael, AJ, Kellam, P, Adamson, WE, Carman, WF, Griffiths, MJ, O'Garra, A and Openshaw, PJM (2018) Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza. Nature Immunology, 19 (06). pp. 625-635.

Text Openshaw_MOSAIC final_V5_151973716_1_referenced clean_+table1_noSuppLegends_authorfix.docx - Author Accepted Manuscript Download (75kB)

Abstract

© 2018 The Author(s). 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:	Article
Uncontrolled Keywords:	MOSAIC Investigators, Neutrophils, Humans, Disease Progression, Interferons, RNA, Messenger, Adolescent, Adult, Aged, Middle Aged, Female, Male, Influenza, Human, Young Adult, Transcriptome, Biomarkers
Depositing User:	Symplectic Admin
Date Deposited:	05 Jul 2018 16:03
Last Modified:	19 Jan 2023 01:31
DOI:	10.1038/s41590-018-0111-5
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3023402