| First Author | Saz-Leal P | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 5 | Pages | 1118-1126 |
| PubMed ID | 30380404 | Mgi Jnum | J:271059 |
| Mgi Id | MGI:6278387 | Doi | 10.1016/j.celrep.2018.09.092 |
| Citation | Saz-Leal P, et al. (2018) Targeting SHIP-1 in Myeloid Cells Enhances Trained Immunity and Boosts Response to Infection. Cell Rep 25(5):1118-1126 |
| abstractText | 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 (LysMDeltaSHIP-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 LysMDeltaSHIP-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. |
