Macrophages can hand lipids directly to natural killer cells during contact, and the transferred fats suppress the killer cells’ production of interferon-gamma, according to a study from Trinity College Dublin published in Nature Communications. The work identifies a metabolic circuit in which one immune cell type restrains another without a cytokine signal.
Natural killer cells are the rapid-response units of innate immunity, capable of killing infected or malignant cells within hours of encountering them. Their activity is tightly coupled to their metabolism, but far less is understood about how neighboring immune cells shape that metabolic state. The Dublin group, led by David Finlay, found that macrophages stimulated by lipopolysaccharide, a bacterial molecule that mimics infection, induce lipid accumulation inside natural killer cells. The effect appears as a swelling of lipid droplets, the cells’ fat stores, and it suppresses mTORC1, a master regulator of cellular growth and function, along with the production of interferon-gamma.
The fatty acids that accumulate in the natural killer cells are synthesized inside the macrophages, not taken up from the environment. Genetic and pharmacological experiments showed the transfer requires direct cell-cell contact and is associated with movement of the fatty acid transporter CD36 between cells, a process known as trogocytosis, in which one cell acquires fragments of another’s membrane. The macrophages are provisioning, passing along the molecules their target cells will use, and the effect is to put a brake on the killer cells.
The causal chain is rigorously established. Blocking fatty acid synthesis specifically in the macrophages prevents lipid accumulation in the natural killer cells and restores both mTORC1 activity and interferon-gamma production. Remove the contact, block the synthesis, and the suppression disappears. The study defines a feedback circuit: macrophages exposed to bacterial products accumulate lipids and pass them to natural killer cells, which then produce less interferon-gamma, a cytokine that also acts on macrophages, potentially closing the loop.
The findings bear on hyperinflammation, where a mechanism that lets macrophages dampen natural killer cell activity could be part of the body’s attempt to apply the brakes, and on immunotherapy, where blocking the lipid transfer could help keep killer cells active in the tumor microenvironment.
The authors note the experimental context. The core findings come from co-culture systems and in vivo models, and while the direction of the effect is clear, the quantitative importance of this pathway relative to the cytokine-based signals that regulate natural killer cells remains to be determined. The study examined macrophages stimulated by a bacterial product; whether other activation states, or other myeloid cells, use the same mechanism is an open question.
The study adds to a broader rethinking of immune cell communication. The field has long focused on secreted proteins, cytokines and chemokines, as the primary language, but a growing body of work shows that direct contact matters too, through receptor pairs on opposing cell surfaces, and that cells can exchange material, membrane fragments, proteins, and even organelles. The Dublin study adds lipids to that list of exchanged goods and shows that the transfer has functional consequences: the receiving cell changes what it produces. Metabolism is not merely a property of individual cells but a channel of intercellular influence.
Sources: Keane, C., Mayock, S., Corkish, C. et al. Macrophages tune NK cell IFNγ production through direct lipid transfer. Nature Communications (2026). DOI: 10.1038/s41467-026-76444-0.