Metabolic Regulation of NK Cell Antiviral Functions During Cytomegalovirus Infection

Overview

Journal J Leukoc Biol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2023 Feb 27

PMID 36843434

Authors

Maria Cimpean

Megan A Cooper

Affiliations

Soon will be listed here.

Abstract

Natural killer (NK) cells quickly mount cytotoxic responses, produce cytokines, and proliferate in response to infected or transformed cells. Moreover, they can develop memory, with enhanced effector responses following activation, in some cases with antigen specificity. To optimally execute these functions, NK cells undergo metabolic reprogramming. Here, we discuss the interplay between metabolism and NK cell function in the context of viral infections. We review findings supporting metabolic regulation of NK cell effector functions, with a focus on NK cell antiviral infection in the context of cytomegalovirus in the mouse (MCMV) and human (HCMV).

Citing Articles

Nutrient transporter pattern in CD56 NK cells: CD16 (FcγRIIIA)-dependent modulation and association with memory NK cell functional profile.

De Federicis D, Capuano C, Ciuti D, Molfetta R, Galandrini R, Palmieri G Front Immunol. 2024; 15:1477776.

PMID: 39606236 PMC: 11599182. DOI: 10.3389/fimmu.2024.1477776.

Immunology of Cytokine Storm Syndromes: Natural Killer Cells.

French A, Cron R, Cooper M Adv Exp Med Biol. 2024; 1448:145-159.

PMID: 39117813 DOI: 10.1007/978-3-031-59815-9_11.

IL-15 Priming Alters IFN-γ Regulation in Murine NK Cells.

Cimpean M, Keppel M, Gainullina A, Fan C, Sohn H, Schedler N J Immunol. 2023; 211(10):1481-1493.

PMID: 37747317 PMC: 10873103. DOI: 10.4049/jimmunol.2300283.

References

OSullivan T, Sun J, Lanier L . Natural Killer Cell Memory. Immunity. 2015; 43(4):634-45. PMC: 4621966. DOI: 10.1016/j.immuni.2015.09.013. View

Brand A, Singer K, Koehl G, Kolitzus M, Schoenhammer G, Thiel A . LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells. Cell Metab. 2016; 24(5):657-671. DOI: 10.1016/j.cmet.2016.08.011. View

Orange J, Biron C . Characterization of early IL-12, IFN-alphabeta, and TNF effects on antiviral state and NK cell responses during murine cytomegalovirus infection. J Immunol. 1996; 156(12):4746-56. View

Cham C, Gajewski T . Glucose availability regulates IFN-gamma production and p70S6 kinase activation in CD8+ effector T cells. J Immunol. 2005; 174(8):4670-7. DOI: 10.4049/jimmunol.174.8.4670. View

Beziat V, Dalgard O, Asselah T, Halfon P, Bedossa P, Boudifa A . CMV drives clonal expansion of NKG2C+ NK cells expressing self-specific KIRs in chronic hepatitis patients. Eur J Immunol. 2011; 42(2):447-57. DOI: 10.1002/eji.201141826. View

Shi L, Tu B . Acetyl-CoA and the regulation of metabolism: mechanisms and consequences. Curr Opin Cell Biol. 2015; 33:125-31. PMC: 4380630. DOI: 10.1016/j.ceb.2015.02.003. View

Mace E, Orange J . Emerging insights into human health and NK cell biology from the study of NK cell deficiencies. Immunol Rev. 2018; 287(1):202-225. PMC: 6310041. DOI: 10.1111/imr.12725. View

Keating S, Zaiatz-Bittencourt V, Loftus R, Keane C, Brennan K, Finlay D . Metabolic Reprogramming Supports IFN-γ Production by CD56bright NK Cells. J Immunol. 2016; 196(6):2552-60. DOI: 10.4049/jimmunol.1501783. View

Liu L, Landskron J, Ask E, Enqvist M, Sohlberg E, Traherne J . Critical Role of CD2 Co-stimulation in Adaptive Natural Killer Cell Responses Revealed in NKG2C-Deficient Humans. Cell Rep. 2016; 15(5):1088-1099. PMC: 4858565. DOI: 10.1016/j.celrep.2016.04.005. View

10.

Caligiuri M, Zmuidzinas A, Manley T, Levine H, Smith K, Ritz J . Functional consequences of interleukin 2 receptor expression on resting human lymphocytes. Identification of a novel natural killer cell subset with high affinity receptors. J Exp Med. 1990; 171(5):1509-26. PMC: 2187895. DOI: 10.1084/jem.171.5.1509. View

11.

Presti R, Popkin D, Connick M, Paetzold S, Virgin 4th H . Novel cell type-specific antiviral mechanism of interferon gamma action in macrophages. J Exp Med. 2001; 193(4):483-96. PMC: 2195910. DOI: 10.1084/jem.193.4.483. View

12.

Smith H, Heusel J, Mehta I, Kim S, Dorner B, Naidenko O . Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci U S A. 2002; 99(13):8826-31. PMC: 124383. DOI: 10.1073/pnas.092258599. View

13.

Boothby M, Brookens S, Raybuck A, Cho S . Supplying the trip to antibody production-nutrients, signaling, and the programming of cellular metabolism in the mature B lineage. Cell Mol Immunol. 2021; 19(3):352-369. PMC: 8591438. DOI: 10.1038/s41423-021-00782-w. View

14.

Brodin P, Jojic V, Gao T, Bhattacharya S, Lopez Angel C, Furman D . Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015; 160(1-2):37-47. PMC: 4302727. DOI: 10.1016/j.cell.2014.12.020. View

15.

Michelet X, Dyck L, Hogan A, Loftus R, Duquette D, Wei K . Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat Immunol. 2018; 19(12):1330-1340. DOI: 10.1038/s41590-018-0251-7. View

16.

Sheppard S, Santosa E, Lau C, Violante S, Giovanelli P, Kim H . Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function. Cell Rep. 2021; 35(9):109210. PMC: 8221253. DOI: 10.1016/j.celrep.2021.109210. View

17.

French A, Yokoyama W . Natural killer cells and viral infections. Curr Opin Immunol. 2002; 15(1):45-51. DOI: 10.1016/s095279150200002x. View

18.

Russell D, Huang L, VanderVen B . Immunometabolism at the interface between macrophages and pathogens. Nat Rev Immunol. 2019; 19(5):291-304. PMC: 7032560. DOI: 10.1038/s41577-019-0124-9. View

19.

Marchingo J, Sinclair L, Howden A, Cantrell D . Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation. Elife. 2020; 9. PMC: 7056270. DOI: 10.7554/eLife.53725. View

20.

Sheppard S, Sun J . Virus-specific NK cell memory. J Exp Med. 2021; 218(4). PMC: 7992500. DOI: 10.1084/jem.20201731. View