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

Suzanne L. Cole; Jake Dunning; Wai Ling Kok; Kambez Hajipouran Benam; Adel Benlahrech; Emmanouela Repapi; Fernando O. Martinez; Lydia Drumright; Timothy J. Powell; Michael Bennett; Ruth Elderfield; Catherine Thomas; Tao Dong; John McCauley; Foo Y. Liew; Stephen Taylor; Maria Zambon; Wendy Barclay; Vincenzo Cerundolo; Peter J. Openshaw; Andrew J. McMichael; MOSAIC Investigators; Ling-Pei Ho; Fernando Oneissi Martinez Estrada

doi:10.1172/jci.insight.91868

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

Suzanne L. Cole, Jake Dunning, Wai Ling Kok, Kambez Hajipouran Benam, Adel Benlahrech, Emmanouela Repapi, Fernando O. Martinez, Lydia Drumright, Timothy J. Powell, Michael Bennett, …

JCI insight, Vol.2(7), pp.e91868-e91868

06/04/2017

DOI: https://doi.org/10.1172/jci.insight.91868

PMCID: PMC5374077

PMID: 28405622

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. In a cohort of influenza patients, previously healthy and young patients who succumbed to life-threatening disease were defined by high levels of circulating M1-like, TNF-α hi monocytes.

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Title: M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza
Creators: Suzanne L. Cole - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Jake Dunning - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Wai Ling Kok - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Kambez Hajipouran Benam - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Adel Benlahrech - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Emmanouela Repapi - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Fernando O. Martinez - University of Surrey
Lydia Drumright - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Timothy J. Powell - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Michael Bennett - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Ruth Elderfield - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Catherine Thomas - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Tao Dong - University of Surrey
John McCauley - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Foo Y. Liew - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Stephen Taylor - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Maria Zambon - University of Surrey
Wendy Barclay - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Vincenzo Cerundolo - University of Surrey
Peter J. Openshaw - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Andrew J. McMichael - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
MOSAIC Investigators
Ling-Pei Ho - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. National Heart and Lung Division, Imperial College London, St. Mary’s Campus, London, United Kingdom. Computational Biology Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom. The Francis Crick Institute, London, United Kingdom. Section of Virology, Faculty of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom. National Infection Service, Public Health England, Colindale, London, United Kingdom. The MOSAIC investigators are detailed in the Supplemental Acknowledgments. Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom. School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
Fernando Oneissi Martinez Estrada - School of Biosciences and Medicine
Publication Details: JCI insight, Vol.2(7), pp.e91868-e91868
Publisher: American Society for Clinical Investigation
Date published: 06/04/2017
Identifiers: 99783442502346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

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

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