TY  - JOUR
A1  - Vollmuth, Nadine
A1  - Schlicker, Lisa
A1  - Guo, Yongxia
A1  - Hovhannisyan, Pargev
A1  - Janaki-Raman, Sudha
A1  - Kurmasheva, Naziia
A1  - Schmitz, Werner
A1  - Schulze, Almut
A1  - Stelzner, Kathrin
A1  - Rajeeve, Karthika
A1  - Rudel, Thomas
T1  - c-Myc plays a key role in IFN-γ-induced persistence of Chlamydia trachomatis
JF  - eLife
N2  - 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-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.
KW  - Chlamydia trachomatis
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301385
VL  - 11
ER  -