Indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2 activity and severe course of COVID-19

also on behalf of the Amsterdam UMC COVID-19 Biobank Study Group

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

COVID-19 is a pandemic with high morbidity and mortality. In an autopsy cohort of COVID-19 patients, we found extensive accumulation of the tryptophan degradation products 3-hydroxy-anthranilic acid and quinolinic acid in the lungs, heart, and brain. This was not related to the expression of the tryptophan-catabolizing indoleamine 2,3-dioxygenase (IDO)-1, but rather to that of its isoform IDO-2, which otherwise is expressed rarely. Bioavailability of tryptophan is an absolute requirement for proper cell functioning and synthesis of hormones, whereas its degradation products can cause cell death. Markers of apoptosis and severe cellular stress were associated with IDO-2 expression in large areas of lung and heart tissue, whereas affected areas in brain were more restricted. Analyses of tissue, cerebrospinal fluid, and sequential plasma samples indicate early initiation of the kynurenine/aryl-hydrocarbon receptor/IDO-2 axis as a positive feedback loop, potentially leading to severe COVID-19 pathology.

Original languageEnglish (US)
Pages (from-to)256-261
Number of pages6
JournalJournal of Pathology
Volume256
Issue number3
DOIs
StatePublished - Mar 2022

Keywords

  • apoptosis
  • autophagy
  • brain
  • heart
  • innate_immune_response
  • lungs
  • nucleus_of_cranial_nerve_X
  • skeletal_muscle
  • tryptophan

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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