NK Cells from Human Cytomegalovirus–Seropositive Individuals Have a Distinct Metabolic Profile That Correlates with Elevated mTOR Signaling
Year: 2023
Type: article
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.
Source: The Journal of Immunology
Institution: University of Minnesota
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: Medical Scientist Training Program, G4103018608, Viral priming and targeting NK cells against solid tumor malignancies, G9000062357, G9000278143, G9000327612, Bcl11b: A Master Transcription Factor Controlling Human NK Cell Development, NK cells, their receptors and cancer therapy, Off-the-Shelf Immune Effector Cells for Hematological Malignancies, Targeting off-the-shelf iPSC-derived natural killer cells against solid tumors
OpenAlex ID: W4381470413