Frontiers in Immunology (Feb 2024)

Potent induction of trained immunity by Saccharomyces cerevisiae β-glucans

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

DOI
https://doi.org/10.3389/fimmu.2024.1323333
Journal volume & issue
Vol. 15

Abstract

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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.

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