Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza
Dunning J., Blankley S., Hoang LT., Cox M., Graham CM., James PL., Bloom CI., Chaussabel D., Banchereau J., Brett SJ., 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., Gordon SB., Hussell T., Thompson C., Zambon MC., Baillie KJ., Hume DA., Simmonds P., Hayward A., Smyth RL., McNamara PS., Semple MG., Nguyen-Van-Tam JS., Ho LP., McMichael AJ., Kellam P., Adamson WE., Carman WF., Griffiths MJ., Moffatt MF., O'Garra A., Openshaw PJM.
© 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.