Stimulated macrophages suppress natural killer cell immune functions by transferring synthesized lipids directly into them, according to research published in Nature Communications.
Researchers observed that lipopolysaccharide-stimulated macrophages induce lipid accumulation inside natural killer (NK) cells. This metabolic shift increases the presence of lipid droplets within NK cells, using fatty acids produced inside the macrophages. The accumulation suppresses mTORC1 activity and halts the production of interferon-gamma (IFNγ), a key effector molecule in innate immune responses.
Laboratory tests using co-culture and in vivo models demonstrated that fatty acid transfer requires direct cell-to-cell contact. Genetic and pharmacological assays confirmed that this movement of lipids associates with the transfer of the CD36 protein between cells through trogocytosis.
Scientists selectively blocked fatty acid synthesis inside macrophages to evaluate the metabolic feedback circuit. Inhibiting this pathway stopped lipid accumulation in neighboring NK cells, which restored mTORC1 activity and returned IFNγ production to functional levels.
David K. Finlay and Cathal Keane led the research alongside investigators from Trinity College Dublin, University College Dublin, and Weill Cornell Medicine. Research Ireland, Enterprise Ireland, and the European Union's Marie Skłodowska-Curie Actions funded the study, which was accepted on July 23, 2026, and published on August 8, 2026.
