Learning from other diseases: protection and pathology in chronic fungal infections

Fungal commensals coexist in a complex milieu of bacteria within the human body. An increased understanding of the importance of microbiota in shaping the host’s immune and metabolic activities has rendered fungal interactions with their hosts more complex than previously appreciated. Metagenomics has revealed the complex interactions between fungal and bacterial commensals that, either directly or through the participation of the host immune system, impact on immune homeostasis at mucosal surfaces that, in turn, lead to secondary fungal infections. Metabolomics has captured the dialogue between the mammalian host and its microbiota. It appears that the host tryptophan catabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO1) plays a dominant role in the interplay between tryptophan catabolism by microbial communities, the host’s own pathway of metabolite production, and the activation of the aryl hydrocarbon receptor (AhR)/IL-22 axis, eventually impacting on mucosal immune homeostasis and host/fungal symbiosis. Thus, the regulatory loop involving AhR and IDO1 may be exploited for the development of multi-pronged host- and microbiota-directed therapeutic approaches for mucosal and systemic fungal diseases.