M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza
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
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
View: Text | PDF
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

×

Figure 5

Blood monocytes and lung monocyte/macrophages are M1 like.

Options: View larger image (or click on image) Download as PowerPoint
Blood monocytes and lung monocyte/macrophages are M1 like. (A–C) Number ...
(A–C) Number of M1 and M2 monocytes/MDMs on day 3 in blood, BAL, and lung digests. M1 monocytes were defined as CD86+Ly6Chi cells and M2 monocytes as CD206+Ly6Chi in appropriate gates from Figure 4, B–E. 2 experiments; n = 6 mice in total. (D and E) TNF-α production measured by flow cytometry intracellular cytokine staining after 6 hours of LPS in blood and ex vivo in lungs. Gated on Ly6Chi monocytes from blood. Statistical significance measured using 1-way ANOVA with Tukey test. Horizontal lines and error bars in graphs represent mean ± SEM for normally distributed sets and median ± interquartile range for nonnormal distribution. *P < 0.05; **P < 0.01; ****P < 0.0001. BAL, bronchoalveolar lavage; MDM, monocyte-derived macrophage.