PMID- 34077722
OWN - NLM
STAT- MEDLINE
DCOM- 20220211
LR  - 20240226
IS  - 2211-1247 (Electronic)
VI  - 35
IP  - 9
DP  - 2021 Jun 1
TI  - Reliance on Cox10 and oxidative metabolism for antigen-specific NK cell 
      expansion.
PG  - 109209
LID - S2211-1247(21)00558-1 [pii]
LID - 10.1016/j.celrep.2021.109209 [doi]
AB  - Natural killer (NK) cell effector functions are dependent on metabolic regulation 
      of cellular function; however, less is known about in vivo metabolic pathways 
      required for NK cell antiviral function. Mice with an inducible NK-specific 
      deletion of Cox10, which encodes a component of electron transport chain complex 
      IV, were generated to investigate the role of oxidative phosphorylation in NK 
      cells during murine cytomegalovirus (MCMV) infection. Ncr1-Cox10(Delta/Delta) mice had 
      normal numbers of NK cells but impaired expansion of antigen-specific Ly49H(+) NK 
      cells and impaired NK cell memory formation. Proliferation in vitro and 
      homeostatic expansion were intact, indicating a specific metabolic requirement 
      for antigen-driven proliferation. Cox10-deficient NK cells upregulated 
      glycolysis, associated with increased AMP-activated protein kinase (AMPK) and 
      mammalian target of rapamycin (mTOR) activation, although this was insufficient 
      to protect the host. These data demonstrate that oxidative metabolism is required 
      for NK cell antiviral responses in vivo.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Mah-Som, Annelise Y
AU  - Mah-Som AY
AD  - Department of Pediatrics, Division of Rheumatology/Immunology, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Keppel, Molly P
AU  - Keppel MP
AD  - Department of Pediatrics, Division of Rheumatology/Immunology, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Tobin, Joshua M
AU  - Tobin JM
AD  - Department of Pediatrics, Division of Rheumatology/Immunology, Washington 
      University School of Medicine, St. Louis, MO 63110, USA; Medical Scientist 
      Training Program, Washington University School of Medicine, St. Louis, MO 63110, 
      USA.
FAU - Kolicheski, Ana
AU  - Kolicheski A
AD  - Department of Pediatrics, Division of Rheumatology/Immunology, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Saucier, Nermina
AU  - Saucier N
AD  - Department of Pediatrics, Division of Rheumatology/Immunology, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Sexl, Veronika
AU  - Sexl V
AD  - Department of Biomedical Science, University of Veterinary Medicine of Vienna, 
      Vienna, Austria.
FAU - French, Anthony R
AU  - French AR
AD  - Department of Pediatrics, Division of Rheumatology/Immunology, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Wagner, Julia A
AU  - Wagner JA
AD  - Medical Scientist Training Program, Washington University School of Medicine, St. 
      Louis, MO 63110, USA; Department of Medicine, Division of Oncology, Washington 
      University School of Medicine, St. Louis, MO 63110, USA.
FAU - Fehniger, Todd A
AU  - Fehniger TA
AD  - Department of Medicine, Division of Oncology, Washington University School of 
      Medicine, St. Louis, MO 63110, USA.
FAU - Cooper, Megan A
AU  - Cooper MA
AD  - Department of Pediatrics, Division of Rheumatology/Immunology, Washington 
      University School of Medicine, St. Louis, MO 63110, USA. Electronic address: 
      cooper_m@wustl.edu.
LA  - eng
GR  - R01 AI078994/AI/NIAID NIH HHS/United States
GR  - P50 CA171963/CA/NCI NIH HHS/United States
GR  - R01 CA205239/CA/NCI NIH HHS/United States
GR  - T32 GM007200/GM/NIGMS NIH HHS/United States
GR  - UL1 TR000448/TR/NCATS NIH HHS/United States
GR  - P 28571/FWF_/Austrian Science Fund FWF/Austria
GR  - UL1 TR002345/TR/NCATS NIH HHS/United States
GR  - F30 AI129110/AI/NIAID NIH HHS/United States
GR  - P30 CA091842/CA/NCI NIH HHS/United States
GR  - R01 AI127752/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Antigens)
RN  - 0 (Ligands)
RN  - 0 (Membrane Proteins)
RN  - EC 2.5.- (Alkyl and Aryl Transferases)
RN  - EC 2.5.1.- (COX10 protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.4.3 (Adenylate Kinase)
SB  - IM
MH  - Adenylate Kinase/metabolism
MH  - Alkyl and Aryl Transferases/deficiency/*metabolism
MH  - Animals
MH  - Antigens/*metabolism
MH  - Cell Proliferation
MH  - Cytomegalovirus Infections/immunology/pathology/virology
MH  - Enzyme Activation
MH  - Gene Deletion
MH  - Immunologic Memory
MH  - Killer Cells, Natural/*cytology/enzymology/*metabolism
MH  - Ligands
MH  - Membrane Proteins/deficiency/*metabolism
MH  - Mice, Inbred C57BL
MH  - Muromegalovirus/physiology
MH  - Oxidation-Reduction
MH  - Phenotype
MH  - RNA-Seq
MH  - Single-Cell Analysis
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Mice
PMC - PMC8229496
MID - NIHMS1710594
OTO - NOTNLM
OT  - Cox10
OT  - NK cells
OT  - metabolism
OT  - murine cytomegalovirus
OT  - oxidative phosphorylation
OT  - proliferation
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2021/06/03 06:00
MHDA- 2022/02/12 06:00
PMCR- 2021/06/25
CRDT- 2021/06/02 20:07
PHST- 2020/08/14 00:00 [received]
PHST- 2021/03/08 00:00 [revised]
PHST- 2021/05/11 00:00 [accepted]
PHST- 2021/06/02 20:07 [entrez]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2022/02/12 06:00 [medline]
PHST- 2021/06/25 00:00 [pmc-release]
AID - S2211-1247(21)00558-1 [pii]
AID - 10.1016/j.celrep.2021.109209 [doi]
PST - ppublish
SO  - Cell Rep. 2021 Jun 1;35(9):109209. doi: 10.1016/j.celrep.2021.109209.