Fungal chitin induces trained immunity in human monocytes during cross-talk with Saccharomyces cerevisiae

Objectives: Candida albicans, a common colonizer of the human mucosa, is able to train innate immune cells in a process mediated by the β-glucans present in the cell wall1. Saccaromyces cerevisiae is another constant but harmful colonizer of humans and recently it has been demonstrated to be even more abundant than C. albicans2. The aim of this study was to investigate the in vitro training properties of S.cerevisiae on innate immune cells and the relation occurring between the cell wall composition and the observed effect. Methods: S. cerevisiae isolates from diverse ecological niches have been tested for their ability to induce trained immunity on human monocytes. The cell wall sugar composition of the S. cerevisiae strains have been investigated through ion-exchange chromatography. Glucan, mannan and chitin have been extracted from the yeast cell wall and tested independently for their capabilities to induce immune response. Results: The S. cerevisiae clinical isolates were able to strongly enhance pro-inflammatory cytokine production when monocytes were exposed to a secondary bacterial or fungal stimulus. Among cell wall components a higher content of chitin was detected in S. cerevisiae clinical isolates. Chitin was able alone to induce a potent immune response in terms of IL-6 and TNFα and to enhance the phagocytic killing by monocytes. Conclusions: The study gives novel prespective on how S.cerevisiae, a passenger microorganism present from centuries in our foods, could help priming organismal protection against pathogens. The chitin-induced training immunity suggests the importance of yeast cell wall modulation in protecting from dysbiosis.