c-Myc plays a key role in IFN-γ-induced persistence of Chlamydia trachomatis
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-301385
- Chlamydia trachomatis (Ctr) can persist over extended times within their host cell and thereby establish chronic infections. One of the major inducers of chlamydial persistence is interferon-gamma (IFN-γ) released by immune cells as a mechanism of immune defence. IFN-γ activates the catabolic depletion of L-tryptophan (Trp) via indoleamine-2,3-dioxygenase (IDO), resulting in persistent Ctr. Here, we show that IFN-γ induces the downregulation of c-Myc, the key regulator of host cell metabolism, in a STAT1-dependent manner. Expression of c-MycChlamydia trachomatis (Ctr) can persist over extended times within their host cell and thereby establish chronic infections. One of the major inducers of chlamydial persistence is interferon-gamma (IFN-γ) released by immune cells as a mechanism of immune defence. IFN-γ activates the catabolic depletion of L-tryptophan (Trp) via indoleamine-2,3-dioxygenase (IDO), resulting in persistent Ctr. Here, we show that IFN-γ induces the downregulation of c-Myc, the key regulator of host cell metabolism, in a STAT1-dependent manner. Expression of c-Myc rescued Ctr from IFN-γ-induced persistence in cell lines and human fallopian tube organoids. Trp concentrations control c-Myc levels most likely via the PI3K-GSK3β axis. Unbiased metabolic analysis revealed that Ctr infection reprograms the host cell tricarboxylic acid (TCA) cycle to support pyrimidine biosynthesis. Addition of TCA cycle intermediates or pyrimidine/purine nucleosides to infected cells rescued Ctr from IFN-γ-induced persistence. Thus, our results challenge the longstanding hypothesis of Trp depletion through IDO as the major mechanism of IFN-γ-induced metabolic immune defence and significantly extends the understanding of the role of IFN-γ as a broad modulator of host cell metabolism.…
Autor(en): | Nadine Vollmuth, Lisa Schlicker, Yongxia Guo, Pargev Hovhannisyan, Sudha Janaki-Raman, Naziia Kurmasheva, Werner Schmitz, Almut Schulze, Kathrin Stelzner, Karthika Rajeeve, Thomas Rudel |
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URN: | urn:nbn:de:bvb:20-opus-301385 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften |
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | eLife |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 11 |
Aufsatznummer: | e76721 |
Originalveröffentlichung / Quelle: | eLife (2022) 11:e76721. https://doi.org/10.7554/eLife.76721 |
DOI: | https://doi.org/10.7554/eLife.76721 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Freie Schlagwort(e): | Chlamydia trachomatis |
Datum der Freischaltung: | 02.05.2023 |
EU-Projektnummer / Contract (GA) number: | ERC-2018-ADG/NCI-CAD |
OpenAIRE: | OpenAIRE |
Sammlungen: | Open-Access-Publikationsfonds / Förderzeitraum 2022 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |