TY - JOUR
T1 - Inflammatory and glycolytic programs underpin a primed blood neutrophil state in patients with pneumonia
AU - Schuurman, Alex R.
AU - Butler, Joe M.
AU - Michels, Erik H. A.
AU - Otto, Natasja A.
AU - Brands, Xanthe
AU - Haak, Bastiaan W.
AU - Uhel, Fabrice
AU - Klarenbeek, Augustijn M.
AU - Faber, Daniël R.
AU - Schomakers, Bauke V.
AU - van Weeghel, Michel
AU - de Vos, Alex F.
AU - Scicluna, Brendon P.
AU - Houtkooper, Riekelt H.
AU - Wiersinga, W. Joost
AU - van der Poll, Tom
N1 - Funding Information: We would like to acknowledge the patients and volunteers that have made this investigation possible. This work was supported by ZonMw (grants 40-00812-98-14016, 50-53000-98-139 and 522008011), and the European Union's Horizon 2020 program (grant agreement 847422 – ImmunoSep—and grant agreement 847786 - FAIR). Conceptualization: T.vd.P. W.J.W. B.P.S. Methodology: R.H. B.S. A.K. Formal analysis: A.R.S. J.B. E.M. Investigation: A.R.S. N.O. B.W.H. X.B. A.K. F.U. D.F. Resources: T.vd.P. B.P.S. W.J.W. A.d.V, D.F. Data curation: A.R.S. B.S. J.B. Writing – original draft: A.R.S. T.vd.P. Writing – review and editing: A.R.S. T.vd.P. J.B. E.M. Visualization: A.R.S. J.B. E.M. Supervision: T.vd.P. W.J.W. A.d.V. Project administration: A.R.S. Funding acquisition: T.vd.P, B.P.S. W.J.W. All authors have read and reviewed the manuscript. The authors declare no competing interests. Funding Information: We would like to acknowledge the patients and volunteers that have made this investigation possible. This work was supported by ZonMw (grants 40-00812-98-14016 , 50-53000-98-139 and 522008011 ), and the European Union’s Horizon 2020 program (grant agreement 847422 – ImmunoSep —and grant agreement 847786 - FAIR ). Publisher Copyright: © 2023 The Authors
PY - 2023/7/21
Y1 - 2023/7/21
N2 - Neutrophils are potent immune cells with key antimicrobial functions. Previous in vitro work has shown that neutrophil effector functions are mainly fueled by intracellular glycolysis. Little is known about the state of neutrophils still in the circulation in patients during infection. Here, we combined flow cytometry, stimulation assays, transcriptomics, and metabolomics to investigate the link between inflammatory and metabolic pathways in blood neutrophils of patients with community-acquired pneumonia. Patients’ neutrophils, relative to neutrophils from age- and sex- matched controls, showed increased degranulation upon ex vivo stimulation, and portrayed distinct upregulation of inflammatory transcriptional programs. This neutrophil phenotype was accompanied by a high-energy state with increased intracellular ATP content, and transcriptomic and metabolic upregulation of glycolysis and glycogenolysis. One month after hospital admission, these metabolic and transcriptomic changes were largely normalized. These data elucidate the molecular programs that underpin a balanced, yet primed state of blood neutrophils during pneumonia.
AB - Neutrophils are potent immune cells with key antimicrobial functions. Previous in vitro work has shown that neutrophil effector functions are mainly fueled by intracellular glycolysis. Little is known about the state of neutrophils still in the circulation in patients during infection. Here, we combined flow cytometry, stimulation assays, transcriptomics, and metabolomics to investigate the link between inflammatory and metabolic pathways in blood neutrophils of patients with community-acquired pneumonia. Patients’ neutrophils, relative to neutrophils from age- and sex- matched controls, showed increased degranulation upon ex vivo stimulation, and portrayed distinct upregulation of inflammatory transcriptional programs. This neutrophil phenotype was accompanied by a high-energy state with increased intracellular ATP content, and transcriptomic and metabolic upregulation of glycolysis and glycogenolysis. One month after hospital admission, these metabolic and transcriptomic changes were largely normalized. These data elucidate the molecular programs that underpin a balanced, yet primed state of blood neutrophils during pneumonia.
KW - Health sciences
KW - Immunology
KW - Medicine
UR - http://www.scopus.com/inward/record.url?scp=85164744013&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.isci.2023.107181
DO - https://doi.org/10.1016/j.isci.2023.107181
M3 - Article
C2 - 37496676
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 7
M1 - 107181
ER -