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M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza.

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Title: M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza.
Authors: Cole, SL
Dunning, J
Kok, WL
Benam, KH
Benlahrech, A
Repapi, E
Martinez, FO
Drumright, L
Powell, TJ
Bennett, M
Elderfield, R
Thomas, C
MOSAIC investigators
Dong, T
McCauley, J
Liew, FY
Taylor, S
Zambon, M
Barclay, W
Cerundolo, V
Openshaw, PJ
McMichael, AJ
Ho, LP
Item Type: Journal Article
Abstract: In each influenza season, a distinct group of young, otherwise healthy individuals with no risk factors succumbs to life-threatening infection. To better understand the cause for this, we analyzed a broad range of immune responses in blood from a unique cohort of patients, comprising previously healthy individuals hospitalized with and without respiratory failure during one influenza season, and infected with one specific influenza A strain. This analysis was compared with similarly hospitalized influenza patients with known risk factors (total of n = 60 patients recruited). We found a sustained increase in a specific subset of proinflammatory monocytes, with high TNF-α expression and an M1-like phenotype (independent of viral titers), in these previously healthy patients with severe disease. The relationship between M1-like monocytes and immunopathology was strengthened using murine models of influenza, in which severe infection generated using different models (including the high-pathogenicity H5N1 strain) was also accompanied by high levels of circulating M1-like monocytes. Additionally, a raised M1/M2 macrophage ratio in the lungs was observed. These studies identify a specific subtype of monocytes as a modifiable immunological determinant of disease severity in this subgroup of severely ill, previously healthy patients, offering potential novel therapeutic avenues.
Issue Date: 6-Apr-2017
Date of Acceptance: 23-Feb-2017
URI: http://hdl.handle.net/10044/1/48142
DOI: https://dx.doi.org/10.1172/jci.insight.91868
ISSN: 2379-3708
Publisher: American Society for Clinical Investigation
Journal / Book Title: JCI Insight
Volume: 2
Issue: 7
Copyright Statement: © 2017 Cole et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Wellcome Trust
Medical Research Council (MRC)
Wellcome Trust
Wellcome Trust
Wellcome Trust
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
National Institute for Health Research
Commission of the European Communities
Medical Research Council (MRC)
Funder's Grant Number: 062177/Z/00Z
071381/Z/03/Z
083567/Z/07/Z
MRC Ref G0400503
087805/Z/08/Z
090382/Z/09/Z
090382/Z/09/Z
RDA06 79560
NF-SI-0513-10150
IS-HPU-1112-10064
602525
MR/R502121/1
Publication Status: Published
Conference Place: United States
Article Number: e91868
Appears in Collections:National Heart and Lung Institute
Department of Medicine
Faculty of Medicine



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