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

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.

Authors: Cole SL, Dunning J, Kok WL, Benam KH, Benlahrech A, Repapi E, Martinez FO, Drumright L, Powell TJ, Bennett M, Elderfield R, Thomas C; MOSAIC investigators., Dong T, McCauley J, Liew FY, Taylor S, Zambon M, Barclay W, Cerundolo V, Openshaw PJ, McMichael AJ
Journal: JCI Insight. 2017 Apr 6;2(7):e91868.
Year: 2017
PubMed: Find in PubMed