Human airway macrophages are metabolically reprogrammed by IFN-γ resulting in glycolysis-dependent functional plasticity

Airway macrophages (AM) are the predominant immune cells in the lung and play a crucial role in preventing infection, making them a target for host-directed therapy. Macrophage effector functions are associated with cellular metabolism. A knowledge gap remains in understanding metabolic reprogramming and functional plasticity of distinct human macrophage subpopulations, especially in lung resident AM. We examined tissue-resident AM and monocyte-derived macrophages (MDM; as a model of blood-derived macrophages) in their resting state and after priming with IFN-γ or IL-4 to model the Th1/Th2 axis in the lung. Human macrophages, regardless of origin, had a strong induction of glycolysis in response to IFN-γ or upon stimulation. IFN-γ significantly enhanced cellular energetics in both AM and MDM by upregulating both glycolysis and oxidative phosphorylation. Upon stimulation, AM does not decrease oxidative phosphorylation, unlike MDM which shifts to “Warburg”-like metabolism. IFN-γ priming p..., Metabolic Flux Analysis (Seahorse XFe 24), Flow Cytometry and ELISA., , # **Human airway macrophages are metabolically reprogrammed by IFN-γ resulting in glycolysis-dependent functional plasticity**

[https://doi.org/10.5061/dryad.98sf7m0t5](https://doi.org/10.5061/dryad.98sf7m0t5)

## Description of the data and file structure

The data is presented in a single Excel file. All data in a column on each tab of the Excel file is matched to the same donor. Data is not matched across Excel tabs i.e., different donors may have been used for different experiments due to limitations in cellular yield from samples. It is highly recommended to read the Excel file in conjunction with each figure within the associated paper. The data has been organised based on the layout of figures in the associated eLife paper.

This data consists of human alveolar macrophages and human monocyte-derived macrophages which were left unprimed or primed with IFN-γ or IL-4 (both 10 ng/ml) for 24h. Both cell types were then left unstimulated or stimulated with irradiated Mycobacterium tub...