AUTHOR=Wu Zhelin , Yang Yanjian , Li Jiadong , Bossier Peter , Wei Xiayi , Guo Zheng , Han Biao , Ye Jianmin 

TITLE=β-Glucans in particulate and solubilized forms elicit varied immunomodulatory and apoptosis effects in teleost macrophages in a dosedependent manner

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1243358

DOI=10.3389/fimmu.2023.1243358

ISSN=1664-3224

ABSTRACT=<p>β-Glucans are a group of heterogeneous glucose polymers that possess immunomodulatory activities. The complex nature of their structures, uncertainty regarding the doses, and variable immune effects pose a challenge to comprehensive understanding. In this study, we investigated the immune responses and apoptosis effects in Nile tilapia (<italic>Oreochromis niloticus</italic>) head kidney macrophages (MФ) upon exposure to two β-Glucans (Paramylon and Laminarin) at low and high doses. Our results demonstrate that Paramylon elicits more robust immune responses than Laminarin, albeit with a dose-limiting effect. We also observed that the high-dose Paramylon induces apoptosis, whereas no such effect was detected in Laminarin treatment. Mechanistically, high-dose Paramylon activates the intrinsic apoptosis pathway, with significantly up-regulation of intrinsic apoptosis-related genes and impaired mitochondrial function. On the other hand, Laminarin triggers metabolic reprogramming in MФ, resulting in the enrichment of the metabolite α-Ketoglutarate, which protects the MФ from apoptosis. Overall, our findings highlight the importance of identifying the optimal dose range for β-Glucans, based on sources or structures, to achieve maximal immunomodulatory effects. These results have important implications for the design and optimization of β-Glucans-based drugs or adjuvants in immunotherapies.</p>