Tryptophan catabolism reflects disease activity in human tuberculosis
Jeffrey M. Collins, … , Henry M. Blumberg, Thomas R. Ziegler
Jeffrey M. Collins, … , Henry M. Blumberg, Thomas R. Ziegler
Published May 21, 2020; First published May 5, 2020
Citation Information: JCI Insight. 2020;5(10):e137131. https://doi.org/10.1172/jci.insight.137131.
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Research Article Infectious disease Metabolism

Tryptophan catabolism reflects disease activity in human tuberculosis

Abstract

There is limited understanding of the role of host metabolism in the pathophysiology of human tuberculosis (TB). Using high-resolution metabolomics with an unbiased approach to metabolic pathway analysis, we discovered that the tryptophan pathway is highly regulated throughout the spectrum of TB infection and disease. This regulation is characterized by increased catabolism of tryptophan to kynurenine, which was evident not only in active TB disease but also in latent TB infection (LTBI). Further, we found that tryptophan catabolism is reversed with effective treatment of both active TB disease and LTBI in a manner commensurate with bacterial clearance. Persons with active TB and LTBI also exhibited increased expression of indoleamine 2,3-dioxygenase-1 (IDO-1), suggesting IDO-1 mediates observed increases in tryptophan catabolism. Together, these data indicate IDO-1–mediated tryptophan catabolism is highly preserved in the human response to Mycobacterium tuberculosis and could be a target for biomarker development as well as host-directed therapies.

Authors

Jeffrey M. Collins, Amnah Siddiqa, Dean P. Jones, Ken Liu, Russell R. Kempker, Azhar Nizam, N. Sarita Shah, Nazir Ismail, Samuel G. Ouma, Nestani Tukvadze, Shuzhao Li, Cheryl L. Day, Jyothi Rengarajan, James C.M. Brust, Neel R. Gandhi, Joel D. Ernst, Henry M. Blumberg, Thomas R. Ziegler

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Figure 6

Whole blood transcriptomics demonstrates increased IDO-1 transcription in HIV-negative and HIV-positive persons with active TB disease and LTBI.

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Whole blood transcriptomics demonstrates increased IDO-1 transcription i...
The bubble plots represent whole blood measurement of transcriptional changes in the tryptophan catabolic enzyme IDO-1 in HIV-negative persons (left box) and HIV-positive persons (right box). Study accession numbers from the publicly available National Center for Biotechnology Information’s Gene Expression Omnibus (GEO) data repository are shown on the x axis, and each comparison is shown on the y axis. The color scale for each dot represents the log2 fold change in expression for persons with active TB disease (ATB) and LTBI relative to healthy controls (HC) and person with diseases other than TB and no evidence of infection with M. tuberculosis (OD). The dot size represents the –log P value for each comparison. ‡studies that were performed in children.