{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:18:07Z","timestamp":1788952687919,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":183,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["220211"],"award-info":[{"award-number":["220211"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>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\u2010like differentiation in bacterial infections remains elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we utilise our established NK cell memory assay to investigate the metabolic requirement for memory\u2010like NK cell formation and function in response to the Gram\u2010negative intracellular bacteria <jats:italic>Burkholderia pseudomallei<\/jats:italic> (BP), the causative agent of melioidosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that CD160<jats:sup>+<\/jats:sup> memory\u2010like NK cells upon BP stimulation upregulate glucose and amino acid transporters in a cohort of recovered melioidosis patients which is maintained at least 3\u2010month post\u2010hospital admission. Using an <jats:italic>in vitro<\/jats:italic> assay, human BP\u2010specific CD160<jats:sup>+<\/jats:sup> memory\u2010like 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\u2010stimulation. Antigen\u2010specific and cytokine\u2010induced IFN\u2010\u03b3 production of this memory\u2010like NK cell subset are highly dependent on oxidative phosphorylation (OXPHOS) with some dependency on glycolysis, whereas the formation of CD160<jats:sup>+<\/jats:sup> memory\u2010like NK cells <jats:italic>in vitro<\/jats:italic> is dependent on fatty acid oxidation and OXPHOS and further increased by metformin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study reveals the link between metabolism and cellular function of memory\u2010like NK cells, which can be exploited for vaccine design and for monitoring protection against Gram\u2010negative bacterial 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