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

File Description SizeFormat 
JCI Insight91868.pdfPublished version1.68 MBAdobe PDFDownload
Title: M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza
Author(s): Cole, SL
Dunning, J
Kok, WL
Benam, KH
Benlahrech, A
Repapi, E
Martinez, FO
Drumright, L
Powell, TJ
Bennett, M
Elderfield, R
Thomas, C
Dong, T
McCauley, J
Liew, FY
Taylor, S
Zambon, M
Barclay, W
Cerundolo, V
Openshaw, PJ
McMichael, AJ
Ho, L
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.
Publication Date: 6-Apr-2017
URI: http://hdl.handle.net/10044/1/49715
DOI: https://dx.doi.org/10.1172/jci.insight.91868
ISSN: 2379-3708
Publisher: The 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
Wellcome Trust
Wellcome Trust
GlaxoSmithKline Services Unlimited
National Institute for Health Research
National Institute for Health Research
Commission of the European Communities
Commission of the European Communities
Medical Research Council (MRC)
Funder's Grant Number: 071381/Z/03/Z
083567/Z/07/Z
087805/Z/08/Z
090382/Z/09/Z
090382/Z/09/Z
Nasal LPS
NF-SI-0513-10150
IS-HPU-1112-10064
602525
116019
MR/R502121/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
NKT CELLS REDUCE
VIRUS-INFECTION
A VIRUS
ALVEOLAR MACROPHAGES
PANDEMIC INFLUENZA
IMMUNE-PATHOLOGY
DENDRITIC CELLS
LUNG
PATHOGENESIS
ACTIVATION
Appears in Collections:National Heart and Lung Institute
Repository Tools



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons