Single-cell metabolomics reveals infection-specific metabolic reprogramming of human macrophages

During intracellular infection, host cells adopt different metabolic states that traditional bulk analyses cannot distinguish. Using single-cell spatial metabolomics of human macrophages infected with Legionella pneumophila, we show that bacterial uptake activates host metabolism, whereas the bacterial effectors secreted through the type IV secretion system counteract this response and promote a glycolytic shift. The activity of effectors also generates distinct metabolic states within the infected macrophage population.