Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/96246
Title: Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis
Authors: Cheng, Shih-Chin
Scicluna, Brendon P.
Arts, Rob J.W.
Gresnigt, Mark S.
Lachmandas, Ekta
Giamarellos-Bourboulis, Evangelos J.
Kox, Matthijs
Manjeri, Ganesh R.
Wagenaars, Jori A. L.
Cremer, Olaf L.
Leentjens, Jenneke
Meer, Anne-Jan van der
Veerdonk, Frank L. van de
Bonten, Marc M.J.
Schultz, Marcus J.
Willems, Peter H. G. M.
Pickkers, Peter
Joosten, Leo A.B.
Poll, Tom van der
Netea, Mihai G.
Keywords: Adenosine triphosphate -- Metabolism
Antifungal agents -- Research -- Methodology
Aspergillosis
Cytokines
Endotoxins -- Analysis
Energy metabolism
Escherichia coli infections -- Diagnosis
Immunological tolerance
Septicemia -- Diagnosis
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Cheng, S. C., Scicluna, B. P., Arts, R. J., Gresnigt, M. S., Lachmandas, E., Giamarellos-Bourboulis, E. J., ... & Netea, M. G. (2016). Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis. Nature Immunology, 17(4), 406-413.
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.
URI: https://www.um.edu.mt/library/oar/handle/123456789/96246
Appears in Collections:Scholarly Works - FacHScABS

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