M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza
Suzanne L. Cole, … , Andrew J. McMichael, Ling-Pei Ho
Suzanne L. Cole, … , Andrew J. McMichael, Ling-Pei Ho
Published April 6, 2017
Citation Information: JCI Insight. 2017;2(7):e91868. https://doi.org/10.1172/jci.insight.91868.
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Research Article Immunology Infectious disease

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

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, MOSAIC investigators, Tao Dong, John McCauley, Foo Y. Liew, Stephen Taylor, Maria Zambon, Wendy Barclay, Vincenzo Cerundolo, Peter J. Openshaw, Andrew J. McMichael, Ling-Pei Ho

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Figure 1

Flow chart of patient recruitment and grouping.

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Flow chart of patient recruitment and grouping. All patients with suspec...
All patients with suspected influenza A virus (IAV) infection (influenza-like symptoms) were sampled at TP1. aTechnical quality control (QC) required that all samples were processed without any freeze-thaw cycles, all baseline “fluorescence minus one” FACS controls were present, and control fluorochromes were at the expected intensity on the day of acquisition. bComorbidities in the study were hematological malignancies, asthma, chronic obstructive pulmonary disease (COPD), diabetes mellitus, cardiac failure, ischemic heart disease, and cancers. Patients with hypertension were not excluded. TP, time point; WRF, with risk factors; NRF, no risk factors.