Commensal yeast S. cerevisiae trains human monocytes for a heightened cytokine response upon bacterial encounter

The immune system is essential to maintain the mutualistic homeostatic interaction between the host and its micro- and mycobiota. Living as a commensal on human skin and being a passenger in the digestive tract, Saccharomyces cerevisiae could potentially modulate the host immunity and significantly shape the immune response. We observed that diverse S. cerevisiae strains induce trained immunity in monocytes through a strain-dependent manner leading to enhanced cytokine production upon secondary stimulation with TLR ligands and bacterial commensals. These features are reflected by the differences in the pro-inflammatory properties dependent on the origin of the strains, which may be potentially related to the different adaptation to the environment from which they were isolated. We established that even though β-glucan is sufficient to train the innate immunity, S. cerevisiae chitin drives the induction of trained immunity potentiating cytokine modulation and killing ability. This study reveals how commensal and passenger microorganisms could be important in promoting health and preventing mucosal diseases by modulating host defense and regulating the microbiota. Dietary supplementation of specific probiotic microorganisms may be a viable strategy to train a healthy immune system. This work was supported by funding from the European Community’s Integrative Project FP7, SYBARIS (Grant Agreement 242220, www.sybaris.eu) and by funding from Provincia Autonoma di Trento’s Accordo di Programma (METAFOODLABS project).