Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro

Abstract

Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K. marxianus to modulate human dendritic cell (DC) function in vitro. Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K. marxianus as a strong candidate for further development as a novel yeast probiotic.

Production of Fungal Phytases from Agroindustrial Byproducts for Pig Diets

“…Thus, considering the potential of this genus for industrial phytase production, the fungus A. zeae B was selected for further evaluations. The yeast K. marxianus also presents good performance for large scale fermentations 22 and the production of various compounds, such as bioethanol 23,24 , β-galactosidase 25,26 and probiotics 27,28 . Therefore, it was selected as a model strain for phytase production.…”

Description of a Novel Probiotic Concept: Implications for the Modulation of the Immune System

“…In addition, it increases the production of the short-chain fatty acids acetate and propionate (Maccaferri et al, 2012). Kluyveromyces marxianus also modulates human dendritic cell function in vitro and induces a response dominated by Foxp3+ T regulatory lymphocytes (Smith et al, 2016). Such a response may bear positive consequences in those conditions characterized by excessive inflammation or uncontrolled proliferation.…”

Cutting Edge: Probiotics and Fecal Microbiota Transplantation in Immunomodulation

“…Moreover, the expression of Foxp3 and IL-10 in Treg also increased [74]. In addition, research showed that after Kluyveromyces marxianus (a fungus that provides beneficial effects like probiotics) stimulated PBMCs, they found DC secreted more IL-12, IL-1, IL-6, and IL-10, which promoted the polarization of naive T cells to Treg [75].…”

“…Finally, they cultured K. marxianus and S. boulardii with the DC-naive T cell cocultured system; they found that K. marxianus induced the differentiation of naive T cells to Foxp3+ Treg, increased secretion of IL-10, and controlled inflammation. Moreover, S. boulardii could induce differentiation of naive T cells to Th1, resulting in an increased secretion of IFN- γ [75]. Thomas et al cocultured bone marrow-derived DCs from Crohn's disease (CD) and ulcerative colitis (UC) patients with S. boulardii ; they found that DCs secreted less TNF- α but more IL-6 and IL-8 [86].…”