Abstract
Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The concept of individual microorganisms influencing the makeup of T cell subsets via 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 hundreds of non-Saccharomyces yeasts in terms of their interaction with the human gastrointestinal immune system. The aim of the present study was to evaluate 170 yeast strains representing 75 diverse species for modulation of inflammatory cytokine secretion by human DCs in vitro, as compared to cytokine responses induced by a S. boulardii reference strain with probiotic properties documented in clinical trials. Furthermore, we investigated whether cytokine inducing interactions between yeasts and human DCs are dependent upon yeast viability or rather a product of membrane interactions regardless of yeast metabolic function. We demonstrate high diversity in yeast induced cytokine profiles and employ multivariate data analysis to reveal distinct clustering of yeasts inducing similar cytokine profiles in DCs, highlighting clear species distinction within specific yeast genera. The observed differences in induced DC cytokine profiles add to the currently very limited knowledge of the cross-talk between yeasts and human immune cells and provide a foundation for selecting yeast strains for further characterization and development toward potentially novel yeast probiotics. Additionally, we present data to support a hypothesis that the interaction between yeasts and human DCs does not solely depend on yeast viability, a concept which may suggest a need for further classifications beyond the current definition of a probiotic.
Highlights
The mucosal-associated lymphoid tissues lining the human gastrointestinal tract contain a network of immune cells with the important task of distinguishing potentially dangerous antigens from harmless substances
The aim of the present study was to evaluate a broad spectrum of yeasts (170 strains representing 75 diverse yeast species were included in the study) for modulation of inflammatory cytokine secretion by human Dendritic cells (DCs), as compared to cytokine responses induced by a S. boulardii (Ultra-Levure) reference strain with probiotic properties documented in clinical trials [27]
Given that modulation of DC cytokine secretion has been linked to probiotic functionality related to intestinal inflammation, we evaluated yeast modulation of DC secretion of five inflammation related cytokines in vitro
Summary
The mucosal-associated lymphoid tissues lining the human gastrointestinal tract contain a network of immune cells with the important task of distinguishing potentially dangerous antigens from harmless substances. During infection or active inflammation, pathogenic microorganisms bind to pattern recognition receptors expressed by DCs and activate signaling pathways involving MAP kinases and the nuclear transcription factor NFkB resulting in production and secretion of a wide range of chemokines and cytokines with distinct inflammatory effects. In this context, DC secretion of inflammatory cytokines such as TNFa and IL-1b is central for acute, innate inflammatory responses involving attraction of neutrophils and macrophages to the site of infection. Efficient antigen presentation relies upon DC maturation, a process involving upregulation of co-stimulatory surface molecules as well as modulation of chemokine receptor expression
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