Preechanukul, Anucha;
Saiprom, Natnaree;
Rochaikun, Kitilak;
Moonmueangsan, Boonthanom;
Phunpang, Rungnapa;
Ottiwet, Orawan;
Kongphrai, Yuphin;
... Chantratita, Narisara; + view all
(2024)
Metabolic requirements of CD160 expressing memory-like NK cells in Gram-negative bacterial infection.
Clinical & Translational Immunology
, 13
(7)
, Article e1513. 10.1002/cti2.1513.
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Abstract
Objective: Unique metabolic requirements accompany the development and functional fates of immune cells. How cellular metabolism is important in natural killer (NK) cells and their memory-like differentiation in bacterial infections remains elusive. // Methods: Here, we utilise our established NK cell memory assay to investigate the metabolic requirement for memory-like NK cell formation and function in response to the Gram-negative intracellular bacteria Burkholderia pseudomallei (BP), the causative agent of melioidosis. // Results: We demonstrate that CD160+ memory-like NK cells upon BP stimulation upregulate glucose and amino acid transporters in a cohort of recovered melioidosis patients which is maintained at least 3-month post-hospital admission. Using an in vitro assay, human BP-specific CD160+ memory-like NK cells show metabolic priming including increased expression of glucose and amino acid transporters with elevated glucose uptake, increased mTOR activation and mitochondrial membrane potential upon BP re-stimulation. Antigen-specific and cytokine-induced IFN-γ production of this memory-like NK cell subset are highly dependent on oxidative phosphorylation (OXPHOS) with some dependency on glycolysis, whereas the formation of CD160+ memory-like NK cells in vitro is dependent on fatty acid oxidation and OXPHOS and further increased by metformin. // Conclusion: This study reveals the link between metabolism and cellular function of memory-like NK cells, which can be exploited for vaccine design and for monitoring protection against Gram-negative bacterial infection.
| Type: | Article |
|---|---|
| Title: | Metabolic requirements of CD160 expressing memory-like NK cells in Gram-negative bacterial infection |
| Location: | Australia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/cti2.1513 |
| Publisher version: | http://dx.doi.org/10.1002/cti2.1513 |
| Language: | English |
| Additional information: | Copyright © 2024 The Author(s). Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. This is an open access article under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Gram-negative bacterial infection, immunometabolism, melioidosis, NK cell, NK cell memory |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10194358 |
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