2026-10-15T10:14:39Z https://data.mendeley.com/oai

oai:data.mendeley.com/ncbph43m85.3 2022-10-07T10:30:21Z

Lundahl, Mimmi Macrophage Innate Training Induced by IL-4 and IL-13 Activation Enhances OXPHOS Driven Anti-Mycobacterial Responses Mendeley Data This is the dataset pertaining to the article "Macrophage Innate Training Induced by IL-4 and IL-13 Activation Enhances OXPHOS Driven Anti-Mycobacterial Responses". To interpret and follow the data, please refer to the linked article, as each excel sheet corresponds with each named graph/figure. Abstract: Macrophages are a highly adaptive population of innate immune cells. Polarization with IFNγ and LPS into the “classically activated” M1 macrophage enhances pro-inflammatory and microbicidal responses, important for eradicating bacteria such as Mycobacterium tuberculosis. By contrast, “alternatively activated” M2 macrophages, polarized with IL-4, oppose bactericidal mechanisms and allow mycobacterial growth. These activation states are accompanied by distinct metabolic profiles, where M1 macrophages favor near exclusive use of glycolysis, whereas M2 macrophages up-regulate oxidative phosphorylation (OXPHOS). Here we demonstrate that activation with IL-4 and IL-13 counterintuitively induces protective innate memory against mycobacterial challenge. In human and murine models, prior activation with IL-4/13 enhances pro-inflammatory cytokine secretion in response to a secondary stimulation with mycobacterial ligands. In our murine model, enhanced killing capacity is also demonstrated. Despite this switch in phenotype, IL-4/13 trained murine macrophages do not demonstrate M1-typical metabolism, instead retaining heightened use of OXPHOS. Moreover, inhibition of OXPHOS with oligomycin, 2-deoxy glucose or BPTES all impeded heightened pro-inflammatory cytokine responses from IL-4/13 trained macrophages. Lastly, this work identifies that IL-10 attenuates protective IL-4/13 training, impeding pro-inflammatory and bactericidal mechanisms. In summary, this work provides new and unexpected insight into alternative macrophage activation states in the context of mycobacterial infection. Immunology Immunometabolism Tuberculosis Macrophage Response Mitermite, Morgane Ryan, Dylan Case, Sarah Williams, Niamh Yang, Ming Lynch, Roisin Lagan, Eimear Lebre, Filipa Gorman, Aoife Stojkovic, Bojan Bracken, Adrian Frezza, Christian Sheedy, Frederick Scanlan, Eoin O'Neill, Luke Gordon, Stephen Lavelle, Ed Dataset doi:10.17632/ncbph43m85.3 oai:data.mendeley.com/ncbph43m85.3 Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 https://data.mendeley.com/datasets/ncbph43m85 2022-10-07T10:30:21Z