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NK Cells from Human Cytomegalovirus-Seropositive Individuals Have a Distinct Metabolic Profile That Correlates with Elevated mTOR Signaling.
Lozada, John R; Zhang, Bin; Miller, Jeffrey S; Cichocki, Frank.
Afiliação
  • Lozada JR; Department of Medicine, University of Minnesota, Minneapolis, MN.
  • Zhang B; Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN.
  • Miller JS; Department of Medicine, University of Minnesota, Minneapolis, MN.
  • Cichocki F; Department of Medicine, University of Minnesota, Minneapolis, MN.
J Immunol ; 211(4): 539-550, 2023 08 15.
Article em En | MEDLINE | ID: mdl-37341510
ABSTRACT
CMV can elicit adaptive immune features in both mouse and human NK cells. Mouse Ly49H+ NK cells expand 100- to 1000-fold in response to mouse CMV infection and persist for months after exposure. Human NKG2C+ NK cells also expand after human CMV (HCMV) infection and persist for months. The clonal expansion of adaptive NK cells is likely an energy-intensive process, and the metabolic requirements that support adaptive NK cell expansion and persistence remain largely uncharacterized. We previously reported that NK cells from HCMV-seropositive donors had increased maximum capacity for both glycolysis and mitochondrial oxidative phosphorylation relative to NK cells from HCMV-seronegative donors. In this article, we report an extension of this work in which we analyzed the metabolomes of NK cells from HCMV-seropositive donors with NKG2C+ expansions and NK cells from HCMV seronegative donors without such expansions. NK cells from HCMV+ donors exhibited striking elevations in purine and pyrimidine deoxyribonucleotides, along with moderate increases in plasma membrane components. Mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that, as a part of mTOR complex 1 (mTORC1), bridges nutrient signaling to metabolic processes necessary for cell growth. Signaling through mTORC1 induces both nucleotide and lipid synthesis. We observed elevated mTORC1 signaling on activation in both NKG2C- and NKG2C+ NK cells from HCMV+ donors relative to those from HCMV- donors, demonstrating a correlation between higher mTORC1 activity and synthesis of key metabolites for cell growth and division.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Citomegalovirus / Citomegalovirus Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Citomegalovirus / Citomegalovirus Idioma: En Ano de publicação: 2023 Tipo de documento: Article