Cole, SL, Dunning, J, Kok, WL, Benam, KH, Benlahrech, A, Repapi, E, Martinez, FO, Drumright, L, Powell, TJ, Bennett, M 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).
ISSN 2379-3708
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 |
---|---|
Depositing User: | Symplectic Admin |
Date Deposited: | 30 Jun 2017 12:55 |
Last Modified: | 19 Jan 2023 07:01 |
DOI: | 10.1172/jci.insight.91868 |
Open Access URL: | https://insight.jci.org/articles/view/91868/pdf |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3008270 |
Available Versions of this Item
- M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza. (deposited 30 Jun 2017 12:55) [Currently Displayed]