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

Cole, S. L. et al. (2017) M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza. JCI Insight, 2(7), e91868. (doi: 10.1172/jci.insight.91868) (PMID:28405622) (PMCID:PMC5374077)

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.

• Item Type: Articles
• Additional Information: The study was funded by the Wellcome Trust and the Medical Research Council (MRC) (program no. U117585868 and U117512723; project grant G0600371). LPH was a Higher Education Funding Council for England Senior Fellow, and SLC was a recipient of an MRC studentship. The MRC UK and Wellcome Trust funded MOSAIC via program grant 090382/Z/09/Z and via Imperial College’s Comprehensive Biomedical Research Centre.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liew, Prof Foo
• Authors: Cole, S. L., Dunning, J., Kok, W. L., Benam, K. H., Benlahrech, A., Repapi, E., Martinez, F. O., Drumright, L., Powell, T. J., Bennett, M., Elderfield, R., Thomas, C., Dong, T., McCauley, J., Liew, F. Y., Taylor, S., Zambon, M., Barclay, W., Cerundolo, V., Openshaw, P. J., McMichael, A. J., and Ho, L.-P.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: JCI Insight
• Publisher: American Society for Clinical Investigation
• ISSN: 2379-3708
• ISSN (Online): 2379-3708
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in JCI Insight 2(7): e91868
• Publisher Policy: Reproduced under a Creative Commons License