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

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Cole, Suzanne L, Dunning, Jake, Kok, Wai Ling, Benam, Kambez Hajipouran, Benlahrech, Adel, Repapi, Emmanouela, Martinez, Fernando O, Drumright, Lydia, Powell, Timothy J, Bennett, Michael et al (show 12 more authors) , Elderfield, Ruth, Thomas, Catherine, Dong, Tao, McCauley, John, Liew, Foo Y, Taylor, Stephen, Zambon, Maria, Barclay, Wendy, Cerundolo, Vincenzo, Openshaw, Peter J, McMichael, Andrew J and Ho, Ling-Pei (2017) M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza. JCI INSIGHT, 2 (7). e91868-.

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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:	Article
Uncontrolled Keywords:	Infectious Diseases, Influenza, Pneumonia & Influenza, Rare Diseases, Emerging Infectious Diseases, Vaccine Related, Prevention, Clinical Research, 2.1 Biological and endogenous factors, 2 Aetiology, 2.2 Factors relating to the physical environment, Infection, Inflammatory and immune system, Adult, Aged, Animals, Female, Humans, Influenza A Virus, H5N1 Subtype, Influenza, Human, Lung, Macrophages, Male, Mice, Mice, Inbred C57BL, Middle Aged, Monocytes, Phenotype, Tumor Necrosis Factor-alpha, Viral Load, Young Adult
Depositing User:	Symplectic Admin
Date Deposited:	06 Sep 2017 15:20
Last Modified:	16 Mar 2024 15:53
DOI:	10.1172/jci.insight.91868
Open Access URL:	https://insight.jci.org/articles/view/91868/pdf
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3009275

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• M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza. (deposited 30 Jun 2017 12:55)
  • M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza. (deposited 06 Sep 2017 15:20) [Currently Displayed]