title: Microbiota control of a tryptophan-AhR pathway in disease tolerance to fungi.
abstract: 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. The aryl hydrocarbon receptor (AhR) has a pivotal role in connecting tryptophan catabolism by microbial communities and the host's own pathway of tryptophan metabolite production with the orchestration of T-cell function. AhR activation by a Lactobacillus-derived AhR ligand leads to the production of IL-22 to the benefit of mucosal defense mechanisms, an activity upregulated in the absence of the host tryptophan catabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO1), which is required for protection from fungal diseases ("disease tolerance"). As AhR activation in turn leads to the activation-in a feedback fashion-of IDO1, the regulatory loop involving AhR and IDO1 may have driven the coevolution of commensal fungi with the mammalian immune system and the microbiota, to the benefit of host survival and fungal commensalism. This review will discuss the essential help the microbiota provides in controlling the balance between the dual nature of the fungal-host relationship, namely, commensalism vs. infection.
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
authors.forename: Teresa
authors.initials: T
authors.lastname: Zelante
authors.forename: Antonella
authors.initials: A
authors.lastname: De Luca
authors.forename: Rossana G
authors.initials: RG
authors.lastname: Iannitti
authors.forename: Silvia
authors.initials: S
authors.lastname: Moretti
authors.forename: Andrea
authors.initials: A
authors.lastname: Bartoli
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.forename: Paolo
authors.initials: P
authors.lastname: Puccetti
mesh_terms: D005658:Fungi / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D007778:Lactobacillus / Q000378:metabolism; D064307:Microbiota; D009181:Mycoses / Q000276:immunology*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D013559:Symbiosis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014364:Tryptophan / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007378:Interleukins; D018336:Receptors, Aryl Hydrocarbon; D014364:Tryptophan; D000097043:Interleukin-22; C576710:IDO1 protein, human
keywords: Aryl hydrocarbon receptor; IL-22; Indoleamine 2,3-dioxygenase 1; Microbiota; Mycobiome; Tryptophan