Department of Experimental Immunology, Amsterdam University Medical Centers (UMC) and Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, The Netherlands.
Department of Pathology, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands.
J Pathol. 2022 Mar;256(3):256-261. doi: 10.1002/path.5842. Epub 2022 Jan 10.
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. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd on behalf of The Pathological Society of Great Britain and Ireland.
COVID-19 是一种高发病率和死亡率的大流行疾病。在一项 COVID-19 患者的尸检队列研究中，我们发现肺部、心脏和大脑中色氨酸降解产物 3-羟基邻氨基苯甲酸和喹啉酸大量积聚。这与色氨酸分解吲哚胺 2,3-双加氧酶 (IDO)-1 的表达无关，而是与它的同工酶 IDO-2 的表达有关，而 IDO-2 通常很少表达。色氨酸的生物利用度是细胞正常功能和激素合成的绝对要求，而其降解产物会导致细胞死亡。在肺和心脏组织的大片区域中，与 IDO-2 表达相关的细胞凋亡和严重的细胞应激标志物，而在大脑中受影响的区域则更局限。对组织、脑脊液和连续血浆样本的分析表明，色氨酸降解产物作为正反馈回路，可能导致严重的 COVID-19 病理，导致犬尿氨酸/芳基烃受体/IDO-2 轴的早期启动。
