Potent induction of trained immunity by Saccharomyces cerevisiae β-glucans
Patricia Vuscan, Brenda Kischkel, Aikaterini Hatzioannou, Efrosyni Markaki, Andrei Sarlea, María Tintoré, Jordi Cuñé, Panayotis Verginis, Carlos de Lecea, Triantafyllos Chavakis, Leo A. B. Joosten, Mihai G. Netea
Abstract
Candida albicans cell wall component β-glucan has been extensively studied for its ability to induce epigenetic and functional reprogramming of innate immune cells, a process termed trained immunity . We show that a high-complexity blend of two individual β-glucans from Saccharomyces cerevisiae possesses strong bioactivity, resulting in an enhanced trained innate immune response by human primary monocytes. The training required the Dectin-1/CR3, TLR4, and MMR receptors, as well as the Raf-1, Syk, and PI3K downstream signaling molecules. By activating multiple receptors and downstream signaling pathways, the components of this β-glucan preparation are able to act synergistically, causing a robust secondary response upon an unrelated challenge. In in-vivo murine models of melanoma and bladder cell carcinoma, pre-treatment of mice with the β-glucan preparation led to a significant reduction in tumor growth. These insights may aid in the development of future therapies based on β-glucan structures that induce an effective trained immunity response.