Indoleamine 2,3-dioxygenases (IDOs) degrade l-tryptophan to kynurenines and drive the de novo synthesis of nicotinamide adenine dinucleotide. Unsurprisingly, various invertebrates, vertebrates, and even fungi produce IDO. In mammals, IDO1 also serves as a homeostatic regulator, modulating immune response to infection via local tryptophan deprivation, active catabolite production, and non-enzymatic cell signaling. Whether fungal Idos have pleiotropic functions that impact on host-fungal physiology is unclear. Here, we show that Aspergillus fumigatus possesses three ido genes that are expressed under conditions of hypoxia or tryptophan abundance. Loss of these genes results in increased fungal pathogenicity and inflammation in a mouse model of aspergillosis, driven by an alternative tryptophan degradation pathway to indole derivatives and the host aryl hydrocarbon receptor. Fungal tryptophan metabolic pathways thus cooperate with the host xenobiotic response to shape host-microbe interactions in local tissue microenvironments.

Bioceros 3584 Utrecht the Netherlands

Department of Medical Microbiology and Immunology Department of Bacteriology University of Wisconsin Madison WI USA

Department of Medical Microbiology Centre of Expertise in Mycology Radboud University Medical Centre Nijmegen the Netherlands

Department of Medicine and Surgery University of Perugia 06132 Perugia Italy

Interdepartmental Centre for Measures G Casnati University of Parma Parco Area delle Scienze 23 A 43124 Parma Italy

Mass Spectrometry Centre University of Florence 50019 Florence Italy

MRC Centre for Medical Mycology Aberdeen Fungal Group Institute of Medical Sciences University of Aberdeen Aberdeen AB25 2ZD UK

P4T group Department of Food and Drug University of Parma Parco Area delle Scienze 27 A 43124 Parma Italy

Research Centre for Toxic Compounds in the Environment Brno Czech Republic

Singapore Immunology Network Singapore Singapore

Unitè des Aspergillus Pasteur Institute 75724 Paris France

Zobrazit více v PubMed

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