Saz-Leal, Pauladel Fresno, CarlosBrandi, PaolaMartinez-Cano, SaraiDungan, Otto M.Chisholm, John D.Kerr, William G.Sancho, David2018-11-222018-11-222018Cell Rep. 2018; 25(5):1118-11262211-1247http://hdl.handle.net/20.500.12105/6661beta-Glucan-induced trained immunity in myeloid cells leads to long-term protection against secondary infections. Although previous studies have characterized this phenomenon, strategies to boost trained immunity remain undefined. We found that beta-glucan-trained macrophages from mice with a myeloid-specific deletion of the phosphatase SHIP-1 (LysM Delta SHIP-1) showed enhanced proinflammatory cytokine production in response to lipopolysaccharide. Following beta-glucan training, SHIP-1-deficient macrophages exhibited increased phosphorylation of Akt and mTOR targets, correlating with augmented glycolytic metabolism. Enhanced training in the absence of SHIP-1 relied on histone methylation and acetylation. Trained LysM Delta SHIP-1 mice produced increased amounts of proinflammatory cytokines upon rechallenge in vivo and were better protected against Candida albicans infection compared with control littermates. Pharmacological inhibition of SHIP-1 enhanced trained immunity against Candida infection in mouse macrophages and human peripheral blood mononuclear cells. Our data establish proof of concept for improvement of trained immunity and a strategy to achieve it by targeting SHIP-1.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/CANDIDA-ALBICANS INFECTIONIN-VIVOINNATE IMMUNITYMONOCYTESPROTECTIONINFLAMMATIONREINFECTIONINDUCTIONVITROAttribution-NonCommercial-NoDerivatives 4.0 Internacional30380404251118-112610.1016/j.celrep.2018.09.092Cell Reportsopen access