170: Mechanisms behind immunoregulatory effects of probiotic yeasts

The concept of individual microorganisms influencing the makeup of T cell subsets through interactions with intestinal dendritic cells (DCs) appears to constitute the foundation for immunoregulatory effects of probiotics, and several studies have reported probiotic strains resulting in reduction of intestinal inflammation through modulation of DC function. Consequent to a focus on Saccharomyces boulardii as the fundamental probiotic yeast, very little is known about non- Saccharomyces yeasts in terms of their interaction with the human gastrointestinal immune system. We evaluated the immune stimulating capabilities of a diverse selection of non- Saccharomyces yeasts by incubation with human monocyte-derived DCs followed by DC incubation with autologous naive T cells. Quantification of secreted cytokine levels revealed yeasts with highly reproducible and distinct DC and T cell cytokine induction profiles, as compared to the established probiotic S. boulardii . The observed differences in induced cytokine profiles, supported by T cell subset stains, indicate that certain yeasts are capable of inducing an immune response dominated by T reg cells, whereas others appear to induce a more complex adaptive immune response involving T H 1, T H 17, and T reg cells. To explore the mechanisms behind the observed cytokine induction, we blocked relevant DC pattern recognition receptors and investigated the cytokine inducing properties of yeast cell wall extracts. Our data identify the β-glucan receptor Dectin-1 as key for DC recognition of S. boulardii as well as non- Saccharomyces yeasts, initiating downstream signaling pathways leading to the observed DC cytokine profiles. In contrast, TLR2 and DC-SIGN do not appear involved in the recognition. As expected based on the identification of Dectin-1 as involved in yeast recognition, β-glucan containing yeast cell wall extracts induced robust DC cytokine secretion, an observation that parallels recent in vivo findings and appears to support a hypothesis that yeast cell wall components are responsible for the observed modulation of immune cell function.