Aspergillus Fumigatus Tryptophan Metabolic Route Differently Affects Host Immunity

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Jan 27

PMID 33503414

Citations 18

Authors

Teresa Zelante

Tsokyi Choera

Anne Beauvais

Francesca Fallarino

Giuseppe Paolicelli

Giuseppe Pieraccini

Marco Pieroni

Claudia Galosi

Claudia Beato

Antonella De Luca

Francesca Boscaro

Riccardo Romoli

Xin Liu

Adilia Warris

Paul E Verweij

Eloise Ballard

Monica Borghi

Marilena Pariano

Gabriele Costantino

Mario Calvitti

Carmine Vacca

Vasilis Oikonomou

Marco Gargaro

Alicia Yoke Wei Wong

Louis Boon

Marcel den Hartog

Zdenek Spacil

Paolo Puccetti

Jean-Paul Latge

Nancy P Keller

Luigina Romani

Affiliations

Soon will be listed here.

Abstract

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.

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