2026-07-21T08:17:02Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/66612024-09-27T08:11:12Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Saz-Leal, Paula author del Fresno, Carlos author Brandi, Paola author Martinez-Cano, Sarai author Dungan, Otto M. author Chisholm, John D. author Kerr, William G. author Sancho, David author 2018 beta-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. Cell Rep. 2018; 25(5):1118-1126 10.1016/j.celrep.2018.09.092 2211-1247 Cell Reports 30380404 http://hdl.handle.net/20.500.12105/6661 CANDIDA-ALBICANS INFECTION IN-VIVO INNATE IMMUNITY MONOCYTES PROTECTION INFLAMMATION REINFECTION INDUCTION VITRO Targeting SHIP-1 in Myeloid Cells Enhances Trained Immunity and Boosts Response to Infection