4.8 Article

Continuous Exposure to Non-Soluble β-Glucans Induces Trained Immunity in M-CSF-Differentiated Macrophages

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.672796

Keywords

beta-glucan; trained immunity; macrophage model; resilience; dectin-1

Categories

Funding

  1. Danone Nutricia Research
  2. Topsector Agri and Food
  3. Dutch Cancer Society [WUR 2015-7734]
  4. Dutch Ministry of Economic Affairs [KB-23-001-015]
  5. NWO domain Applied and Engineered Sciences

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This study investigates the effects of beta-glucans from different sources on immune cell trained immunity and resilience, showing correlation with activation of the Dectin-1 receptor. However, Dectin-1 receptor activation is not the sole predictor for beta-glucan-mediated trained immunity. The modified in vitro model focuses on macrophage responses and can be applied to assess the potential of dietary polysaccharides to induce trained immunity.
Beta-glucans enable functional reprogramming of innate immune cells, a process defined as trained immunity, which results in enhanced host responsiveness against primary (training) and/or secondary infections (resilience). Trained immunity holds great promise for promoting immune responses in groups that are at risk (e.g. elderly and patients). In this study, we modified an existing in vitro model for trained immunity by actively inducing monocyte-to-macrophage differentiation using M-CSF and applying continuous exposure. This model reflects mucosal exposure to beta-glucans and was used to study the training effects of a variety of soluble or non-soluble beta-glucans derived from different sources including oat, mushrooms and yeast. In addition, trained immunity effects were related to pattern recognition receptor usage, to which end, we analyzed beta-glucan-mediated Dectin-1 activation. We demonstrated that beta-glucans, with different sources and solubilities, induced training and/or resilience effects. Notably, trained immunity significantly correlated with Dectin-1 receptor activation, yet Dectin-1 receptor activation did not perform as a sole predictor for beta-glucan-mediated trained immunity. The model, as validated in this study, adds on to the existing in vitro model by specifically investigating macrophage responses and can be applied to select non-digestible dietary polysaccharides and other components for their potential to induce trained immunity.

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