title: 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.
authors.affiliation: Health & Nutrition Division Discovery, Chr. Hansen A/S, Hørsholm, Denmark.|Department of Food Science, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Ida M
authors.initials: IM
authors.lastname: Smith
authors.affiliation: Health & Nutrition Division Discovery, Chr. Hansen A/S, Hørsholm, Denmark.
authors.forename: Adam
authors.initials: A
authors.lastname: Baker
authors.affiliation: Institute of Metabolic and Cardiovascular Disease, French Institute of Health and Medical Research (INSERM), Toulouse, France.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Christensen
authors.affiliation: CBS-KNAW Fungal Biodiversity Centre, Utrecht, The Netherlands.
authors.forename: Teun
authors.initials: T
authors.lastname: Boekhout
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Frøkiær
authors.affiliation: Department of Food Science, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Arneborg
authors.affiliation: Department of Food Science, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Jespersen
mesh_terms: D002473:Cell Wall / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D020381:Interleukin-17 / Q000032:analysis / Q000378:metabolism; D007716:Kluyveromyces / Q000276:immunology* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D000069983:Saccharomyces boulardii / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D019707:Receptors, Chemokine; D047071:beta-Glucans; D007371:Interferon-gamma