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Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis. / Cheng, Shih-Chin; Scicluna, Brendon P.; Arts, Rob J. W. et al.

In: Nature immunology, Vol. 17, No. 4, 2016, p. 406-413.

Research output: Contribution to journal › Article › Academic › peer-review

Harvard

Cheng, S-C, Scicluna, BP, Arts, RJW, Gresnigt, MS, Lachmandas, E, Giamarellos-Bourboulis, EJ, Kox, M, Manjeri, GR, Wagenaars, JAL, Cremer, OL, Leentjens, J, van der Meer, AJ, van de Veerdonk, FL, Bonten, MJ, Schultz, MJ, Willems, PHGM, Pickkers, P, Joosten, LAB, van der Poll, T & Netea, MG 2016, 'Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis', Nature immunology, vol. 17, no. 4, pp. 406-413. https://doi.org/10.1038/ni.3398

APA

Cheng, S-C., Scicluna, B. P., Arts, R. J. W., Gresnigt, M. S., Lachmandas, E., Giamarellos-Bourboulis, E. J., Kox, M., Manjeri, G. R., Wagenaars, J. A. L., Cremer, O. L., Leentjens, J., van der Meer, A. J., van de Veerdonk, F. L., Bonten, M. J., Schultz, M. J., Willems, P. H. G. M., Pickkers, P., Joosten, L. A. B., van der Poll, T., & Netea, M. G. (2016). Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis. Nature immunology, 17(4), 406-413. https://doi.org/10.1038/ni.3398

Vancouver

Cheng S-C, Scicluna BP, Arts RJW, Gresnigt MS, Lachmandas E, Giamarellos-Bourboulis EJ et al. Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis. Nature immunology. 2016;17(4):406-413. doi: 10.1038/ni.3398

Author

Cheng, Shih-Chin ; Scicluna, Brendon P. ; Arts, Rob J. W. et al. / Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis. In: Nature immunology. 2016 ; Vol. 17, No. 4. pp. 406-413.

BibTeX

@article{ad3baf92dbf249a7b6df5321fbe86edd,
title = "Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis",
abstract = "The acute phase of sepsis is characterized by a strong inflammatory reaction. At later stages in some patients, immunoparalysis may be encountered, which is associated with a poor outcome. By transcriptional and metabolic profiling of human patients with sepsis, we found that a shift from oxidative phosphorylation to aerobic glycolysis was an important component of initial activation of host defense. Blocking metabolic pathways with metformin diminished cytokine production and increased mortality in systemic fungal infection in mice. In contrast, in leukocytes rendered tolerant by exposure to lipopolysaccharide or after isolation from patients with sepsis and immunoparalysis, a generalized metabolic defect at the level of both glycolysis and oxidative metabolism was apparent, which was restored after recovery of the patients. Finally, the immunometabolic defects in humans were partially restored by therapy with recombinant interferon-γ, which suggested that metabolic processes might represent a therapeutic target in sepsis",
author = "Shih-Chin Cheng and Scicluna, {Brendon P.} and Arts, {Rob J. W.} and Gresnigt, {Mark S.} and Ekta Lachmandas and Giamarellos-Bourboulis, {Evangelos J.} and Matthijs Kox and Manjeri, {Ganesh R.} and Wagenaars, {Jori A. L.} and Cremer, {Olaf L.} and Jenneke Leentjens and {van der Meer}, {Anne J.} and {van de Veerdonk}, {Frank L.} and Bonten, {Marc J.} and Schultz, {Marcus J.} and Willems, {Peter H. G. M.} and Peter Pickkers and Joosten, {Leo A. B.} and {van der Poll}, Tom and Netea, {Mihai G.}",
year = "2016",
doi = "10.1038/ni.3398",
language = "English",
volume = "17",
pages = "406--413",
journal = "Nature immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "4",

}

RIS

TY - JOUR

T1 - Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis

AU - Cheng, Shih-Chin

AU - Scicluna, Brendon P.

AU - Arts, Rob J. W.

AU - Gresnigt, Mark S.

AU - Lachmandas, Ekta

AU - Giamarellos-Bourboulis, Evangelos J.

AU - Kox, Matthijs

AU - Manjeri, Ganesh R.

AU - Wagenaars, Jori A. L.

AU - Cremer, Olaf L.

AU - Leentjens, Jenneke

AU - van der Meer, Anne J.

AU - van de Veerdonk, Frank L.

AU - Bonten, Marc J.

AU - Schultz, Marcus J.

AU - Willems, Peter H. G. M.

AU - Pickkers, Peter

AU - Joosten, Leo A. B.

AU - van der Poll, Tom

AU - Netea, Mihai G.

PY - 2016

Y1 - 2016

N2 - The acute phase of sepsis is characterized by a strong inflammatory reaction. At later stages in some patients, immunoparalysis may be encountered, which is associated with a poor outcome. By transcriptional and metabolic profiling of human patients with sepsis, we found that a shift from oxidative phosphorylation to aerobic glycolysis was an important component of initial activation of host defense. Blocking metabolic pathways with metformin diminished cytokine production and increased mortality in systemic fungal infection in mice. In contrast, in leukocytes rendered tolerant by exposure to lipopolysaccharide or after isolation from patients with sepsis and immunoparalysis, a generalized metabolic defect at the level of both glycolysis and oxidative metabolism was apparent, which was restored after recovery of the patients. Finally, the immunometabolic defects in humans were partially restored by therapy with recombinant interferon-γ, which suggested that metabolic processes might represent a therapeutic target in sepsis

AB - The acute phase of sepsis is characterized by a strong inflammatory reaction. At later stages in some patients, immunoparalysis may be encountered, which is associated with a poor outcome. By transcriptional and metabolic profiling of human patients with sepsis, we found that a shift from oxidative phosphorylation to aerobic glycolysis was an important component of initial activation of host defense. Blocking metabolic pathways with metformin diminished cytokine production and increased mortality in systemic fungal infection in mice. In contrast, in leukocytes rendered tolerant by exposure to lipopolysaccharide or after isolation from patients with sepsis and immunoparalysis, a generalized metabolic defect at the level of both glycolysis and oxidative metabolism was apparent, which was restored after recovery of the patients. Finally, the immunometabolic defects in humans were partially restored by therapy with recombinant interferon-γ, which suggested that metabolic processes might represent a therapeutic target in sepsis

U2 - 10.1038/ni.3398

DO - 10.1038/ni.3398

M3 - Article

C2 - 26950237

VL - 17

SP - 406

EP - 413

JO - Nature immunology

JF - Nature immunology

SN - 1529-2908

IS - 4

ER -

ID: 2875274