A systems biology approach to the mutual interaction between yeast and the immune system.

Dendritic cells (DCs) are capable of sensing fungi and then to initiate an appropriate defense against the invading microbe. We studied interactions between host and microorganism by analyzing the transcriptional response of DCs stimulated by the harmless Saccharomyces cerevisiae and of this phagocytosed fungus. Pathway analyses provided insight into the mutual interactions. Of particular interest was the responses elicited by the DC in the fungus, including downregulation of the carbon-compound metabolism, and upregulation of lipid, fatty acid, glyoxylate and tricarboxylic acid cycles. This indicates that the yeast shifts to a starvation mode and induces morphogenetic and autophagic pathways as well as those associated with reshaping cell wall composition, to resist the immune clearance. This yeast response is independent of the presence of virulence traits as the same transcriptional cell reprogramming has also been observed in potentially pathogenic C. albicans hyphae phagocytosed by macrophages. When comparing our results with the previous findings, it appears that the yeast dimorphic switch is only one of the components of the evolutionarily conserved panels of survival strategies elicited by phagocytosis. In conclusion, a systems biology approach, which combines genomics and pathway analyses, provides a powerful strategy to further our understanding of complex host-pathogen interactions and may ultimately define the distinguishing features of pathogenicity and commensalism.