{Reference Type}: Journal Article
{Title}: Metabolic requirements of CD160 expressing memory-like NK cells in Gram-negative bacterial infection.
{Author}: Preechanukul A;Saiprom N;Rochaikun K;Moonmueangsan B;Phunpang R;Ottiwet O;Kongphrai Y;Wapee S;Janon R;Dunachie S;Kronsteiner B;Chantratita N;
{Journal}: Clin Transl Immunology
{Volume}: 13
{Issue}: 7
{Year}: 2024
{Factor}: 6.515
{DOI}: 10.1002/cti2.1513
{Abstract}: UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.