AUTHOR=Vuscan Patricia , Kischkel Brenda , Hatzioannou Aikaterini , Markaki Efrosyni , Sarlea Andrei , Tintoré Maria , Cuñé Jordi , Verginis Panayotis , de Lecea Carlos , Chavakis Triantafyllos , Joosten Leo A.B. , Netea Mihai G. 

TITLE=Potent induction of trained immunity by Saccharomyces cerevisiae β-glucans

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1323333

DOI=10.3389/fimmu.2024.1323333

ISSN=1664-3224

ABSTRACT=<p><italic>Candida albicans</italic> 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 <italic>trained immunity</italic>. We show that a high-complexity blend of two individual β-glucans from <italic>Saccharomyces cerevisiae</italic> 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 <italic>in-vivo</italic> 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.</p>