Publication details

Aspergillus fumigatus tryptophan metabolic route differently affects host immunity

Authors

ZELANTE Teresa CHOERA Tsokyi BEAUVAIS Anne FALLARINO Francesca PAOLICELLI Giuseppe PIERACCINI Giuseppe PIERONI Marco GALOSI Claudia BEATO Claudia DE LUCA Antonella BOSCARO Francesca ROMOLI Riccardo LIU Xin WARRIS Adilia VERWEIJ Paul E. BALLARD Eloise BORGHI Monica PARIANO Marilena COSTANTINO Gabriele CALVITTI Mario VACCA Carmine OIKONOMOU Vasilis GARGARO Marco WONG Alicia Yoke Wei BOON Louis DEN HARTOG Marcel SPÁČIL Zdeněk PUCCETTI Paolo LATGE Jean-Paul KELLER Nancy P. ROMANI Luigina

Year of publication 2021
Type Article in Periodical
Magazine / Source Cell Reports
MU Faculty or unit

Faculty of Science

Citation
Web https://www.sciencedirect.com/science/article/pii/S2211124720316624?via%3Dihub
Doi http://dx.doi.org/10.1016/j.celrep.2020.108673
Keywords aspergillosis; indoles; Aspergillus fumigatus; IDO; tryptophan; AhR; IL-33; NAD; inflammation
Description Indoleamine 2,3-dioxygenases (Ms) 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 !dos 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.
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