ArticleProceedings of the National Academy of Sciences of the United States of America2016
Trypanosoma brucei metabolite indolepyruvate decreases HIF-1α and glycolysis in macrophages as a mechanism of innate immune evasion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- Integrated multi-omics analysis reveals a gut microbiota-tryptophan metabolism axis contributes to sex differences in a β-aminopropionitrile-induced aortic dissection mouse model.Biology of sex differences · 2026Article
- Cell Signaling by Tryptophan Catabolism.Biochemistry · 2026Review
- Parasites as Modulators of Angiogenesis: Implications for Vascular Biology and Pathogenesis.Pathogens (Basel, Switzerland) · 2026Review
- Giardia duodenalis stabilizes HIF-1α and induces glycolytic alterations in intestinal epithelial cells.Scientific reports · 2025Article
- G1 and G2 ApolipoproteinL1 modulate macrophage inflammation and lipid accumulation through the polyamine pathway.bioRxiv : the preprint server for biology · 2025Article
- Evaluating the impact of Xanthoparmelia conspersa extracts on signaling in HeLa cells and exploring their diverse biological activities.Scientific reports · 2024Article
- Cross-Validation of Metabolic Phenotypes in SARS-CoV-2 Infected Subpopulations Using Targeted Liquid Chromatography-Mass Spectrometry (LC-MS).Journal of proteome research · 2024Article
- The intersection of hostMicrobiology and molecular biology reviews : MMBR · 2024Review
- Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts.Virulence · 2023Review
- A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells.The EMBO journal · 2023Article
- M1/M2 macrophages and their overlaps - myth or reality?Clinical science (London, England : 1979) · 2023Article
- Regulatory Functions of Hypoxia in Host-Parasite Interactions: A Focus on Enteric, Tissue, and Blood Protozoa.Microorganisms · 2023Review
- Crosstalk between Metabolite Production and Signaling Activity in Breast Cancer.International journal of molecular sciences · 2023Article
- Hypoxia-induced tracheal elasticity in vector beetle facilitates the loading of pinewood nematode.eLife · 2023Article
- Indole-3-pyruvic acid alleviates rheumatoid arthritis via the aryl hydrocarbon receptor pathway.Annals of translational medicine · 2023Article
- Proteomic analysis reveals changes in the proteome of human THP-1 macrophages infected withFrontiers in cellular and infection microbiology · 2023Article
- Cardiomyocyte infection byFrontiers in cellular and infection microbiology · 2023Article
- Hypoxia Effects onPathogens (Basel, Switzerland) · 2022Article
- TheAntioxidants (Basel, Switzerland) · 2022Article
- Helminth and Host Crosstalk: New Insight Into Treatment of Obesity and Its Associated Metabolic Syndromes.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stage-dependent and can be problematic during the meningoencephalitic stage, where no new therapies have been developed in recent years and the current drugs have a low therapeutic index. There is a need for more effective treatments and a better understanding of how these parasites evade the host immune response will help in this regard. The bloodstream form of T. brucei excretes significant amounts of aromatic ketoacids, including indolepyruvate, a transamination product of tryptophan. This study demonstrates that this process is essential in bloodstream forms, is mediated by a specialized isoform of cytoplasmic aminotransferase and, importantly, reveals an immunomodulatory role for indolepyruvate. Indolepyruvate prevents the LPS-induced glycolytic shift in macrophages. This effect is the result of an increase in the hydroxylation and degradation of the transcription factor hypoxia-inducible factor-1α (HIF-1α). The reduction in HIF-1α levels by indolepyruvate, following LPS or trypanosome activation, results in a decrease in production of the proinflammatory cytokine IL-1β. These data demonstrate an important role for indolepyruvate in immune evasion by T. brucei.
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