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

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) (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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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
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3009275

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