Progression of whole blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in patients with severe influenza
| Autor: | Dunning, J, Blankley, S, Hoang, LT, Cox, M, Graham, CM, James, PL, Bloom, CI, Chaussabel, D, Banchereau, J, Brett, SJ, 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, 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, O'Garra, A, Openshaw, PJM |
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| Přispěvatelé: | Wellcome Trust, National Institute for Health Research, Medical Research Council (MRC), Asthma UK |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Neutrophils Disease DISEASE Procalcitonin Transcriptome Pathogenesis 0302 clinical medicine MARKERS Interferon Immunology and Allergy Medicine MOSAIC Investigators Young adult UNITED-KINGDOM Middle Aged 3. Good health 1107 Immunology 030220 oncology & carcinogenesis Disease Progression Female Life Sciences & Biomedicine medicine.drug Adult Adolescent Immunology CIRCULATION BIOLOGY VIRUS-INFECTION Lung injury Antiviral Agents Article 03 medical and health sciences Young Adult Influenza Human Humans RNA Messenger PROCALCITONIN METAANALYSIS Aged Science & Technology business.industry Human genetics 030104 developmental biology Interferons business LUNG INJURY Biomarkers |
| Zdroj: | Nature immunology Nature Immunology |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | © 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. |
| Databáze: | OpenAIRE |
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