β-Glucan enhances cytotoxic T lymphocyte responses by activation of human monocyte-derived dendritic cells via the PI3K/AKT pathway

Abstract

Purpose: To investigate the effects of β-(1,3/1,6)-d-glucan on dendritic cells (DCs) maturation, cytotoxic T lymphocyte responses and the molecular mechanisms of its transition.

Methods and results: Human monocyte-derived DCs were matured using yeast-derived particulate β-glucan (WGP) or a mix of TNF-α, IL-1β and IL-6 ("Conv mix"). Multicolor flow cytometry was used to study the DCs phenotype and cytotoxic T-lymphocyte priming and differentiation. ELISA and RT-PCR assays were used to evaluate cytokine production. Western blot was used to investigate the signal pathways. WGP-matured DCs functions were compared with those of Conv mix-matured DCs. WGP-matured DCs expressed higher levels of CD11c, CD86, CD40 and HLA-DR; produced higher levels of pro-inflammatory cytokines; and elicited more CTL priming and differentiation than Conv mix-matured DCs. The PI3K/AKT signaling pathway was involved in WGP-induced dendritic cell maturation. Furthermore, WGP-matured DCs significantly increased tumor-specific CTL responses.

Conclusion: Excellent ability of yeast-derived particulate β-glucan to induce DCs maturation and tumor-specific CTL responses explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DCs generated for therapy.

Keywords: Dendritic cells; Immune response; Signal pathway; β-Glucan.